Life Extension Magazine®
Shampoos, pesticides, drinking water, plastics, and vehicle emissions contain cancer-causing toxins that we are exposed to on a daily basis.
These chemicals can ultimately lead to cancer by damaging our DNA and impeding our detoxification pathways.1-4 In a cruel twist, some of these toxins even activate cancer-causing genes that could otherwise have remained dormant.5,6
Today, it is impossible to avoid the constant onslaught of environmental toxins. But what is possible is to equip your body with the tools it needs to identify toxins and remove them from your system before they can cause any damage.
Cruciferous vegetables do just that. They optimize your body’s detoxification system in order to neutralize many of these chemical threats—and maintain the integrity of your DNA in the process.7-9
Decades of research have shown that ingesting cruciferous vegetables can slash risk of cancer by up to 54%.10-18 These findings show reduced risk of virtually every major type of cancer.19-29
In this article, you’ll learn about the specific components of cruciferous vegetables that fight cancer—and, more importantly, you’ll discover how to harness the powers of cruciferous vegetables to maximize their cancer-fighting benefits.Reducing the Effect of Environmental Toxins
Cruciferous vegetables (cabbage family, broccoli, cauliflower, mustard greens, and Brussels sprouts) are some of the most powerful cancer-fighters nature has to offer. Numerous studies have shown that consuming cruciferous vegetables can sharply reduce your risk of cancer.10-18
They’ve been found to be effective against a vast array of cancers including breast, prostate, colon, lung, bladder, ovarian, kidney, and more. Compounds in cruciferous vegetables also have been found to provide long-term anticancer protection even after they’ve been cleared from the body!30,31
No other food group can boast such powerful, broad-reaching anti-cancer benefits. We’ve known for years that people with the highest overall intake of cruciferous vegetables experience a substantial reduction in the risk of many kinds of cancer—now we’re starting to understand why.
Research has shown that the compounds in cruciferous vegetables have the ability to control cancer’s on/off switch.32-35 Essentially, they help fight against cancer either by activating genes that prevent cancer, or by suppressing genes that cause cancer.36,37
Environmental toxins affect the growth and spread of cancer. Pollutants found in air, water, soil, and a large number of industrial products (especially plastics) contain toxins with cancer-causing potential.1-4
Our bodies are equipped with enzyme systems to fight off toxic threats.3,38 Unfortunately, if your enzyme systems aren’t functioning properly, they can have the opposite effect: They can activate those toxins, causing them to become even more lethally carcinogenic. Making matters worse, some toxins suppress protective enzymes, impairing their ability to protect us from cancer.2,7,38-41
That’s where cruciferous compounds come in. Cruciferous compounds help support the key enzyme systems that are so vital for detoxifying your body of harmful, cancer-causing environmental toxins.9,42,43 The result is unprecedented protection from many of the unavoidable cancer-causing toxins we face on a daily basis.
The Most Common Cruciferous Vegetables
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Glucosinolates: Powerful Chemoprevention
Among cruciferous vegetables’ many powerful components, one group stands out. They’re called glucosinolates, which are found in broccoli and broccoli sprouts. They are converted within the body to a number of active constituents that fight cancer through multi-targeted mechanisms.44-47
For example:
- Glucosinolates reduce the carcinogenicity of many environmental toxins by boosting the genetic expression of important detoxifying enzymes.8,48
- They protect DNA from oxidative damage caused by toxins (up to 28% reduction in human research), thereby preventing the initial changes that can lead to cancer.49
- Glucosinolate derivatives encourage cancer cells to commit suicide, and they suppress genes that create the new blood vessels that support rapid growth of tumors.50
- Finally, there’s evidence that glucosinolate derivatives can turn off genes that promote the spread of cancer.50
Because glucosinolates directly affect the function and expression of genes (the epigenetic effect), experts point out that their protective effects are both wide-ranging and long-lasting.50
Human research reveals that higher dietary intakes of glucosinolates are associated with a reduction in prostate cancer risk by 32%.45 Derivatives of the glucosinolates abundant in broccoli sprouts help prevent stomach cancer by killing the H. pylori bacterium. They also reduce symptoms and biomarkers of inflammation in infected individuals.51
It’s important to note that cooking cruciferous vegetables reduces the rate of glucosinolate conversion to active molecules by about 300%, which is one good reason why supplementation may offer a better alternative.52-54
What You Need to Know
Slash Your Cancer Risk with Cruciferous Vegetables
- Environmental toxins are a growing problem, threatening to raise already high rates of preventable cancers.
- While our bodies contain systems capable of detoxifying harmful chemicals, some enzyme systems in fact activate potential carcinogens, making them more, not less, likely to produce malignancy.
- Toxins, radiation, and other forces exert negative epigenetic effects on our chromosomes, potentially revealing cancer-causing genes for activation.
- Phytochemicals from cruciferous vegetables can attack these natural cancer-promoting processes at their root.
- Cruciferous components work together to inhibit toxin-activating enzymes, boost detoxifying enzymes, and reverse negative epigenetic changes in our chromosomes.
- Because many such compounds are inactivated by cooking, consider using a concentrated supplement containing extracts from multiple types of beneficial cruciferous plants.
Indole-3 Carbinol (I3C)
Indole-3-carbinol (I3C) is one of the most widely-studied components of cruciferous vegetables. Studies have shown that it helps fight cancers of the breast, prostate, and reproductive tract, as well as colon and blood cancers.55
In cancers of the reproductive tract, I3C helps prevent the development of tumors by benefitting important ratios of estrogen metabolites such as the 2-hydroxyestrone:16a-hydroxyestrone ratio and 2-hydroxyestrone:estriol ratios.56-58 Note that 2-hydroxyestrone is an estrogen metabolite that seems to protect against cancer, whereas 16-hydroxyestrone may promote cancer.
Treatment with I3C has also been shown to have a positive effect on recurrent respiratory papillomatosis, a precancerous condition that produces growths in the throat and voice-box. Studies show that treatment with I3C completely stops the growth of papilloma in about 33% of patients and reduces the growth rate and need for surgery in another 33% of patients.59,60
I3C is also beneficial in early cervical cancers known as carcinoma in situ. In one study, 50% of the patients receiving 200 mg/day of I3C had complete regression of carcinoma in situ, while none of the patients in the placebo group were found to be free of carcinoma in situ after 12 weeks.61 And in women with a potentially pre-cancerous condition known as vulvar intraepithelial neoplasia, treatment with 200 or 400 mg/day of I3C reduced the size and severity of lesions on the vaginal labia.62
Animal studies of I3C show a reduction in tumor number and size in experimental models of cancers of the breast, lung, and prostate.63-65
Beneficial Anticancer Hormone Effects of Cruciferous Vegetables
Many cancers, especially those of the reproductive tissues, depend on the presence of sex hormones (primarily estrogen and testosterone) to sustain their growth. Therefore, many treatment approaches rely on blocking or reducing levels of sex hormones in cancer victims. The problem is, conventional drugs can cause side effects and may harm reproductive potential. That’s where cruciferous vegetables come in.
Some components of cruciferous vegetables act more gently and by multiple mechanisms to impede the growth of such hormone-dependent cancers, making them an important part of chemoprevention strategies.
Phenethyl isothiocyanate (PEITC), a natural metabolite of glucosinolates from watercress, has been found, for example, to down-regulate androgen receptors, minimizing stimulation of prostate cancer by testosterone.94 3,3’-Diindolylmethane (DIM), another glucosinolate metabolic product, prevents stimulation of prostate cancer cells by both androgens and estrogen.69,95,96
Breast cancers are commonly estrogen-dependent; sulforaphane and indole-3-carbinol (I3C), still other glucosinolate products, decrease the amounts of cancer-stimulating estrogen receptor-alpha molecules present on cells, inhibiting their proliferation.97,98 This effect has been shown to be active in thyroid cancers as well, which are much more common in women than in men.66,99 DIM has a complementary effect, stimulating cancer-suppressing estrogen receptor-beta molecules.100
Finally, a late 2012 study revealed that I3C also induces degradation of the pro-cancer estrogen receptor alpha, and at the same time reduces expression of tumor-promoting insulin-like growth factor receptor-1 in breast cancer cells.101
Thus, a single serving of a complete cruciferous vegetable supplement can protect reproductive tissues from a whole array of harmful hormonal influences, potentially making you much less likely to develop these devastating malignancies.
Di-indolyl-methane (DIM)
The compound DIM is produced in the body following ingestion of glucosinolates derived from cruciferous vegetables. Animal models, basic lab studies, and limited phase 1 clinical trials show that DIM prevents tumors of the prostate, ovary, cervix, and thyroid, as well as several types of leukemia.66-73 DIM also appears to suppress cancer stem cells, the lingering, super-potent cells that can cause a cancer to recur even years after apparently successful treatment.74,75
Like the other components of cruciferous vegetables, DIM induces cancer cell death by apoptosis, inhibits cancer cell growth, slows or stops new blood vessel development in tumors, and can inhibit factors allowing cancer cells to invade healthy tissue.69
Like I3C, DIM helps prevent the growth of estrogen-dependent tumors, such as those of the female breast and reproductive tract, by boosting the ratio of 2-hydroxyestrone:16a-hydroxyestrone.66,76
Studies in mice demonstrate that DIM can completely prevent the progression of pre-cancerous lesions of the cervix, caused by human papilloma virus (HPV), to full-blown cancer.77 In fact, researchers now theorize that DIM could possibly make the human papilloma virus vaccine more effective, so that it could be given to women already infected with the virus. (Currently it is only effective prior to infection.)77 DIM also increases levels of protective interferon gamma in mouse models of cervical cancer.68
Watercress Extract
One particular cruciferous vegetable, watercress, brings together the very best actions of the other cruciferous vegetables and their components we’ve discussed so far. Studies have shown that watercress has a positive effect on lung, colorectal, and prostate cancers.
Watercress is especially rich in another glucosinolate derivative, called phenethyl-isothiocyanate (PEITC).78 PEITC inhibits carcinogen-activating enzymes, induces cancer detoxification enzymes, and protects against DNA damage.78,79 PEITC is also a remarkably specific epigenetic modulator that turns on genes that suppress cancer.80,81
These effects make watercress extracts particularly appealing in the case of some of our most potent environmental carcinogens, such as those found in tobacco smoke.82-84 Watercress and PEITC are also showing promise in other malignancies caused by activated carcinogens, such as colorectal and prostate cancers.85-87
Look for supplements that contain watercress extract, rather than purified PEITC, because the watercress extracts also contain small amounts of other detoxifying enzyme inducers with even greater potency.78 These substances help prevent cancer growth by reducing inflammatory stimuli such as nitric oxide.88
Cancer Risk Reduction by Cruciferous Vegetables
Cancer Type |
Risk Reduction |
Colorectal |
49%13 |
Melanoma Skin Cancer |
46%17 |
Prostate |
42%20 |
Pancreas |
34%19 |
Kidney |
32%15 |
Bladder |
31%11 |
Esophagus |
28%12 |
Ovary |
24%18 |
Lung |
22%16 |
Breast |
17%12 |
Mouth and Throat |
17%12 |
This table shows the reduction in risk for various cancer types, for those consuming the highest versus the lowest amounts of cruciferous vegetables.
How to Get the Most Benefit from Cruciferous Vegetables
In order to get the maximum health benefits from cruciferous vegetables, make sure you’re consuming a variety of them. Every member of the cruciferous family contains a different set of the glucosinolates that help fight cancer.
For example, broccoli, Brussels sprouts, and cabbage are good sources of a glucosinolate called glucoraphanin, the precursor of sulforaphane. Watercress is an excellent source of the glucosinolate gluconasturtiin, the precursor of PEITC. And garden cress, cabbage, and Indian cress are top sources of a glucosinolate known as glucotropaeolin, the precursor of benzyl isothiocyanate (BITC).
Next, make sure they’re not overcooked. Boiling, steaming, and microwaving at high power substantially decreases the bioavailability of cruciferous vegetables’ cancer-fighting compounds.89-92As beneficial for you as cruciferous vegetables are, there are some things you need to be aware of: The glucosinolate content varies greatly even among individual plants of the same type—and even among parts of the same plant. Even these relative concentrations change during the course of a single plant’s growth cycle.93
That’s why, in addition to eating a variety of cruciferous vegetables, it’s important to take a standardized cruciferous compound supplement. A good cruciferous vegetable supplement should contain I3C, DIM, and PEITC—and for even greater impact, should also include extracts of raw broccoli, cabbage, watercress, and other plant compounds such as apigenin.
Extracts that Complement Cruciferous Vegetables
Several plant extracts complement the detoxifying and epigenetic effects of cruciferous vegetables, making them valuable additions to a comprehensive cancer-prevention supplement. The three most potent ones include apigenin, cat’s claw, and rosemary.
- Apigenin is a bioflavonoid found in celery, parsley, and some other plants that has known chemopreventive effects. These include stopping the cell reproductive cycle, inducing cancer cell death by apoptosis, preventing metastasis, and slowing new blood vessel formation.102-105 Clinical studies show that 20 mg/day of apigenin, in combination with 20 mg/day of the green tea extract EGCG, drastically reduced the rate of colon cancer recurrence following surgical treatment (only 7% of treated patients had recurrences, while 47% of the control patients had recurrences).106 Apigenin shows promise in laboratory and animal studies of cancers of the mouth, skin, and pancreas, as well as in leukemia.102,104,107-109
- The second extract that can be used to complement cruciferous compounds is called Cat’s Claw (Uncaria tomentosa). Lab studies have shown that Uncaria extracts are effective against tumor cells from breast, cervical, lung, thyroid, and colon cancers as well as leukemia.110-112 Uncaria extracts contain powerful antioxidants that protect—and can even repair—DNA from environmental damage.113,114 The result is protection from cancer, especially in organs with a rapid rate of cell turnover, such as skin, colon, and lung, where a small amount of DNA damage can have a rapidly accumulating pro-cancer effect. Uncaria extracts reduced reductions in immune function after chemotherapy while inducing programmed cell death (apoptosis) in malignant cells.110,111,115-117
- Rosemary extracts have shown effectiveness in lab studies of colon, skin, and ovarian cancers, and leukemia.118-124 Rosemary is capable of enhancing the ability of the body to rid itself of potential carcinogens.125,126 In addition, rosemary offers remarkable protection against radiation, shielding cells of the blood and gastrointestinal tract in particular from radiation’s ionizing and oxidizing effects.127-130 Rosemary slows or stops DNA damage and tumor cell proliferation, induces apoptosis of tumor cells, and markedly suppresses genes that enable tissue invasion and metastatic spread.118,131-133 Currently, oncologists are giving special attention to the combination of rosemary extracts plus vitamin D3—and for good reason. Together, these supplements promote normal cell differentiation into mature, non-cancerous white blood cells, helping prevent conversion into leukemia cells.124,134
Summary
Environmental toxins are major causes of cancer. They cause damage to our DNA and can activate cancer-causing genes that would otherwise have remained dormant. Although it’s impossible to avoid these toxins, you can arm your body with the tools it needs to identify the toxins and remove them from your system before they can cause any damage.
Cruciferous vegetables neutralize chemical threats by optimizing your body’s detoxification system, by maintaining the integrity of your DNA, and by activating the genes necessary to fight cancer. The result is unprecedented cancer protection from the unavoidable assaults of daily living.
Many of the cruciferous vegetables’ constituents hold up poorly under cooking and processing conditions. That’s why the best way to consistently gain the benefits of cruciferous compounds is to lightly steam the vegetables and/or obtain them in standardized dietary supplements.
If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.
Editor's Note
Science continues to evolve, and new research is published daily. As such, we have a more recent article on this topic: Cancer Risk Reduced with Cruciferous Vegetables
References
- Msiska Z, Pacurari M, Mishra A, Leonard SS, Castranova V, Vallyathan V. DNA double-strand breaks by asbestos, silica, and titanium dioxide: possible biomarker of carcinogenic potential? Am J Respir Cell Mol Biol. 2010 Aug;43(2):210-9.
- Aoki Y, Sato H, Nishimura N, Takahashi S, Itoh K, Yamamoto M. Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. Toxicol Appl Pharmacol. 2001 Jun 15;173(3):154-60.
- Rengasamy A, Barger MW, Kane E, Ma JK, Castranova V, Ma JY. Diesel exhaust particle-induced alterations of pulmonary phase I and phase II enzymes of rats. J Toxicol Environ Health A. 2003 Jan 24;66(2):153-67.
- Available at: http://www.cancer.org/acs/groups/cid/documents/webcontent/003090-pdf.pdf. Accessed on January 3, 2013.
- McClellan RO. Health effects of exposure to diesel exhaust particles. Annu Rev Pharmacol Toxicol. 1987;27:279-300.
- Mrema EJ, Rubino FM, Brambilla G, Moretto A, Tsatsakis AM, Colosio C. Persistent organochlorinated pesticides and mechanisms of their toxicity. Toxicology. 2012 Dec 3.
- Ritz SA, Wan J, Diaz-Sanchez D. Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract. Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L33-9.
- James D, Devaraj S, Bellur P, Lakkanna S, Vicini J, Boddupalli S. Novel concepts of broccoli sulforaphanes and disease: induction of phase II antioxidant and detoxification enzymes by enhanced-glucoraphanin broccoli. Nutr Rev. 2012 Nov;70(11):654-65.
- Tomczyk J, Olejnik A. Sulforaphane--a possible agent in prevention and therapy of cancer. Postepy Hig Med Dosw (Online). 2010 Nov 29;64:590-603.
- Fowke JH, Chung FL, Jin F, et al. Urinary isothiocyanate levels, brassica, and human breast cancer. Cancer Res. 2003;63(14):3980-6.
- Kirsh VA, Peters U, Mayne ST, et al. Prospective study of fruit and vegetable intake and risk of prostate cancer. J Natl Cancer Inst. 2007;99:1200-9.
- Donaldson MS. Nutrition and cancer: a review of the evidence for an anti-cancer diet. Nutr J. 2004;3:19.
- Hayes JD, Kelleher MO, Eggleston IM. The cancer chemopreventive actions of phytochemicals derived from glucosinolates. Eur J Nutr. 2008;47(Suppl 2):73-88.
- Zhang SM, Hunter DJ, Rosner BA, et al. Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin’s lymphoma among women. Cancer Epidemiol Biomarkers Prev. 2000;9:477-85.
- Michaud DS, Spiegelman D, Clinton SK, Rimm EB, Willett WC, Giovannucci EL. Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J Natl Cancer Inst. 1999;91:605-13.
- Cohen JH, Kristal AR, Stanford JL. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000;92:61-8.
- Kolonel LN, Hankin JH, Whittemore AS, et al. Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol Biomarkers Prev. 2000;9:795-804.
- Tang L, Zirpoli GR, Guru K, et al. Consumption of raw cruciferous vegetables is inversely associated with bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2008;17:938-44.
- Talalay P, Fahey JW. Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J Nutr. 2001 Nov;131(11 Suppl):3027S-33S.
- Lin J, Kamat A, Gu J, et al. Dietary intake of vegetables and fruits and the modification effects of GSTM1 and NAT2 genotypes on bladder cancer risk. Cancer Epidemiol Biomarkers Prev. 2009 Jul;18(7):2090-7.
- Bosetti C, Filomeno M, Riso P, et al. Cruciferous vegetables and cancer risk in a network of case-control studies. Ann Oncol. 2012 Aug;23(8):2198-203.
- Yang G, Gao YT, Shu XO, et al. Isothiocyanate exposure, glutathione S-transferase polymorphisms, and colorectal cancer risk. Am J Clin Nutr. 2010 Mar;91(3):704-11.
- Moore LE, Brennan P, Karami S, et al. Glutathione S-transferase polymorphisms, cruciferous vegetable intake and cancer risk in the Central and Eastern European Kidney Cancer Study. Carcinogenesis. 2007 Sep;28(9):1960-4.
- Hsu CC, Chow WH, Boffetta P, et al. Dietary risk factors for kidney cancer in Eastern and Central Europe. Am J Epidemiol. 2007 Jul 1;166(1):62-70.
- Lam TK, Gallicchio L, Lindsley K, et al. Cruciferous vegetable consumption and lung cancer risk: a systematic review. Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):184-95.
- Fortes C, Mastroeni S, Melchi F, et al. A protective effect of the Mediterranean diet for cutaneous melanoma. Int J Epidemiol. 2008 Oct;37(5):1018-29.
- Pan SY, Ugnat AM, Mao Y, Wen SW, Johnson KC. A case-control study of diet and the risk of ovarian cancer. Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1521-7.
- Chan JM, Wang F, Holly EA. Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area. Cancer Epidemiol Biomarkers Prev. 2005 Sep;14(9):2093-7.
- Joseph MA, Moysich KB, Freudenheim JL, et al. Cruciferous vegetables, genetic polymorphisms in glutathione S-transferases M1 and T1, and prostate cancer risk. Nutr Cancer. 2004;50(2):206-13.
- Bergström P, Andersson HC, Gao Y, et al. Repeated transient sulforaphane stimulation in astrocytes leads to prolonged Nrf2-mediated gene expression and protection from superoxide-induced damage. Neuropharmacology. 2011 Feb-Mar;60(2-3):343-53.
- Dinkova-Kostova AT. Chemoprotection against cancer by isothiocyanates: A focus on the animal models and the protective mechanisms. Top Curr Chem. Epub 2012 Jul 3.
- Banerjee S, Kong D, Wang Z, Bao B, Hillman GG, Sarkar FH. Attenuation of multi-targeted proliferation-linked signaling by 3,3’-diindolylmethane (DIM): from bench to clinic. Mutat Res. 2011 Jul-Oct;728(1-2):47-66.
- Navarro SL, Li F, Lampe JW. Mechanisms of action of isothiocyanates in cancer chemoprevention: an update. Food Funct. 2011 Oct;2(10):579-87.
- Barrera LN, Cassidy A, Johnson IT, Bao Y, Belshaw NJ. Epigenetic and antioxidant effects of dietary isothiocyanates and selenium: potential implications for cancer chemoprevention. Proc Nutr Soc. 2012 May;71(2):237-45.
- Pandey M, Kaur P, Shukla S, Abbas A, Fu P, Gupta S. Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study. Mol Carcinog. 2012 Dec;51(12):952-62.
- Huang J, Plass C, Gerhauser C. Cancer chemoprevention by targeting the epigenome. Curr Drug Targets. 2011 Dec;12(13):1925-56.
- Khan SI, Aumsuwan P, Khan IA, Walker LA, Dasmahapatra AK. Epigenetic events associated with breast cancer and their prevention by dietary components targeting the epigenome. Chem Res Toxicol. 2012 Jan 13;25(1):61-73.
- Leclerc J, Courcot-Ngoubo Ngangue E, Cauffiez C, et al. Xenobiotic metabolism and disposition in human lung: transcript profiling in non-tumoral and tumoral tissues. Biochimie. 2011 Jun;93(6):1012-27.
- Girolami F, Abbadessa G, Racca S, et al. Time-dependent acetylsalicylic acid effects on liver CYP1A and antioxidant enzymes in a rat model of 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinogenesis. Toxicol Lett. 2008 Sep 26;181(2):87-92.
- MacLeod AK, Kelly VP, Higgins LG, et al. Expression and localization of rat aldo-keto reductases and induction of the 1B13 and 1D2 isoforms by phenolic antioxidants. Drug Metab Dispos. 2010 Feb;38(2):341-6.
- Zhang Q, Pi J, Woods CG, Andersen ME. Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses. Toxicol Appl Pharmacol. 2009 Jun 15;237(3):345-56.
- Zhao H, Lin J, Grossman HB, Hernandez LM, Dinney CP, Wu X. Dietary isothiocyanates, GSTM1, GSTT1, NAT2 polymorphisms and bladder cancer risk. Int J Cancer. 2007 May 15;120(10):2208-13.
- Kumar A, Sabbioni G. New biomarkers for monitoring the levels of isothiocyanates in humans. Chem Res Toxicol. 2010 Apr 19;23(4):756-65.
- Shapiro TA, Fahey JW, Dinkova-Kostova AT, et al. Safety, tolerance, and metabolism of broccoli sprout glucosinolates and isothiocyanates: a clinical phase I study. Nutr Cancer. 2006;55(1):53-62.
- Steinbrecher A, Nimptsch K, Husing A, Rohrmann S, Linseisen J. Dietary glucosinolate intake and risk of prostate cancer in the EPIC-Heidelberg cohort study. Int J Cancer. 2009 Nov 1;125(9):2179-86.
- Prakash D, Gupta C. Glucosinolates: the phytochemicals of nutraceutical importance. J Complement Integr Med. 2012;9(1):Article 13.
- Tian M, Bi W, Row KH. Multi-phase Extraction of glycoraphanin from broccoli using aminium ionic liquid-based silica. Phytochem Anal. 2012 Jul 9.
- Nijhoff WA, Grubben MJ, Nagengast FM, et al. Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans. Carcinogenesis. 1995 Sep;16(9):2125-8.
- Verhagen H, Poulsen HE, Loft S, van Poppel G, Willems MI, van Bladeren PJ. Reduction of oxidative DNA-damage in humans by brussels sprouts. Carcinogenesis. 1995 Apr;16(4):969-70.
- Dinkova-Kostova AT. Chemoprotection against cancer by isothiocyanates: A focus on the animal models and the protective mechanisms. Top Curr Chem. 2012 Jul 3.
- Yanaka A, Fahey JW, Fukumoto A, et al. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev Res (Phila). 2009 Apr;2(4):353-60.
- Conaway CC, Getahun SM, Liebes LL, et al. Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli. Nutr Cancer. 2000;38(2):168-78.
- Rouzaud G, Young SA, Duncan AJ. Hydrolysis of glucosinolates to isothiocyanates after ingestion of raw or microwaved cabbage by human volunteers. Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):125-31.
- Rungapamestry V, Duncan AJ, Fuller Z, Ratcliffe B. Effect of meal composition and cooking duration on the fate of sulforaphane following consumption of broccoli by healthy human subjects. Br J Nutr. 2007 Apr;97(4):644-52.
- Aggarwal BB, Ichikawa H. Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle. 2005 Sep;4(9):1201-15. Epub 2005 Sep 6.
- Bradlow HL, Michnovicz JJ, Halper M, Miller DG, Wong GY, Osborne MP. Long-term responses of women to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev. 1994 Oct-Nov;3(7):591-5.
- Michnovicz JJ. Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol. Int J Obes Relat Metab Disord. 1998 Mar;22(3):227-9.
- Reed GA, Peterson KS, Smith HJ, et al. A phase I study of indole-3-carbinol in women: tolerability and effects. Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):1953-60.
- Rosen CA, Woodson GE, Thompson JW, Hengesteg AP, Bradlow HL. Preliminary results of the use of indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998 Jun;118(6):810-5.
- Rosen CA, Bryson PC. Indole-3-carbinol for recurrent respiratory papillomatosis: long-term results. J Voice. 2004 Jun;18(2):248-53.
- Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment of CIN. Gynecol Oncol. 2000 Aug;78(2):123-9.
- Naik R, Nixon S, Lopes A, Godfrey K, Hatem MH, Monaghan JM. A randomized phase II trial of indole-3-carbinol in the treatment of vulvar intraepithelial neoplasia. Int J Gynecol Cancer. 2006 Mar-Apr;16(2):786-90.
- Wu TY, Saw CL, Khor TO, Pung D, Boyanapalli SS, Kong AN. In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate (TRAMP) mice: involvement of Nrf2 and cell cycle/apoptosis signaling pathways. Mol Carcinog. 2012 Oct;51(10):761-70.
- Qian X, Melkamu T, Upadhyaya P, Kassie F. Indole-3-carbinol inhibited tobacco smoke carcinogen-induced lung adenocarcinoma in A/J mice when administered during the post-initiation or progression phase of lung tumorigenesis. Cancer Lett. 2011 Dec 1;311(1):57-65.
- Lubet RA, Heckman BM, De Flora SL, et al. Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: is DIM a substitute for I3C? Oncol Rep. 2011 Sep;26(3):731-6.
- Rajoria S, Suriano R, Parmar PS, et al. 3,3’-diindolylmethane modulates estrogen metabolism in patients with thyroid proliferative disease: a pilot study. Thyroid. 2011 Mar;21(3):299-304.
- Cho HJ, Park SY, Kim EJ, Kim JK, Park JH. 3,3’-Diindolylmethane inhibits prostate cancer development in the transgenic adenocarcinoma mouse prostate model. Mol Carcinog. 2011 Feb;50(2):100-12.
- Sepkovic DW, Raucci L, Stein J, et al. 3,3’-Diindolylmethane increases serum interferon-gamma levels in the K14-HPV16 transgenic mouse model for cervical cancer. In Vivo. 2012 Mar-Apr;26(2):207-11.
- Chen D, Banerjee S, Cui QC, Kong D, Sarkar FH, Dou QP. Activation of AMP-activated protein kinase by 3,3’-diindolylmethane (DIM) is associated with human prostate cancer cell death in vitro and in vivo. PLoS One. 2012;7(10):e47186.
- Gao N, Cheng S, Budhraja A, et al. 3,3’-Diindolylmethane exhibits antileukemic activity in vitro and in vivo through a Akt-dependent process. PLoS One. 2012;7(2):e31783.
- Kandala PK, Srivastava SK. Diindolylmethane-mediated Gli1 protein suppression induces anoikis in ovarian cancer cells in vitro and blocks tumor formation ability in vivo. J Biol Chem. 2012 Aug 17;287(34):28745-54.
- Kandala PK, Wright SE, Srivastava SK. Blocking epidermal growth factor receptor activation by 3,3’-diindolylmethane suppresses ovarian tumor growth in vitro and in vivo. J Pharmacol Exp Ther. 2012 Apr;341(1):24-32.
- Shorey LE, Hagman AM, Williams DE, Ho E, Dashwood RH, Benninghoff AD. 3,3’-Diindolylmethane induces G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia cells. PLoS One. 2012;7(4):e34975.
- Kong D, Heath E, Chen W, et al. Loss of let-7 up-regulates EZH2 in prostate cancer consistent with the acquisition of cancer stem cell signatures that are attenuated by BR-DIM. PLoS One. 2012;7(3):e33729.
- Semov A, Iourtchenco L, Liu LF, et al. Diindolilmethane (DIM) selectively inhibits cancer stem cells. Biochem Biophys Res Commun. 2012 Jul 20;424(1):45-51.
- Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004;50(2):161-7.
- Sepkovic DW, Stein J, Carlisle AD, et al. Results from a dose-response study using 3,3’-diindolylmethane in the K14-HPV16 transgenic mouse model: cervical histology. Cancer Prev Res (Phila). 2011 Jun;4(6):890-6.
- Rose P, Faulkner K, Williamson G, Mithen R. 7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes. Carcinogenesis. 2000 Nov;21(11):1983-8.
- Gill CI, Haldar S, Boyd LA, et al. Watercress supplementation in diet reduces lymphocyte DNA damage and alters blood antioxidant status in healthy adults. Am J Clin Nutr. 2007 Feb;85(2):504-10.
- Wang LG, Liu XM, Fang Y, et al. De-repression of the p21 promoter in prostate cancer cells by an isothiocyanate via inhibition of HDACs and c-Myc. Int J Oncol. 2008 Aug;33(2):375-80.
- Hofmann T, Kuhnert A, Schubert A, et al. Modulation of detoxification enzymes by watercress: in vitro and in vivo investigations in human peripheral blood cells. Eur J Nutr. 2009 Dec;48(8):483-91.
- Hecht SS, Chung FL, Richie JP, Jr., et al. Effects of watercress consumption on metabolism of a tobacco-specific lung carcinogen in smokers. Cancer Epidemiol Biomarkers Prev. 1995 Dec;4(8):877-84.
- Hecht SS. Approaches to chemoprevention of lung cancer based on carcinogens in tobacco smoke. Environ Health Perspect. 1997 Jun;105 Suppl 4:955-63.
- Chung FL, Morse MA, Eklind KI, Xu Y. Inhibition of tobacco-specific nitrosamine-induced lung tumorigenesis by compounds derived from cruciferous vegetables and green tea. Ann N Y Acad Sci. 1993 May 28;686:186-201; discussion 01-2.
- Chung FL, Conaway CC, Rao CV, Reddy BS. Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate. Carcinogenesis. 2000 Dec;21(12):2287-91.
- Chiao JW, Wu H, Ramaswamy G, et al. Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis. 2004 Aug;25(8):1403-8.
- Khor TO, Cheung WK, Prawan A, Reddy BS, Kong AN. Chemoprevention of familial adenomatous polyposis in Apc(Min/+) mice by phenethyl isothiocyanate (PEITC). Mol Carcinog. 2008 May;47(5):321-5.
- Rose P, Won YK, Ong CN, Whiteman M. Beta-phenylethyl and 8-methylsulphinyloctyl isothiocyanates, constituents of watercress, suppress LPS induced production of nitric oxide and prostaglandin E2 in RAW 264.7 macrophages. Nitric Oxide. 2005 Jun;12(4):237-43.
- Shapiro TA, Fahey JW, Wade KL, Stephenson KK, Talalay P. Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol Biomarkers Prev. 2001;10(5):501-8.
- Conaway CC, Getahun SM, Liebes LL, et al. Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli. Nutr Cancer. 2000;38(2):168-78.
- Rungapamestry V, Duncan AJ, Fuller Z, Ratcliffe B. Changes in glucosinolate concentrations, myrosinase activity, and production of metabolites of glucosinolates in cabbage (Brassica oleracea Var. capitata) cooked for different durations. J Agric Food Chem. 2006;54(20):7628-34.
- Rouzaud G, Young SA, Duncan AJ. Hydrolysis of glucosinolates to isothiocyanates after ingestion of raw or microwaved cabbage by human volunteers. Cancer Epidemiol Biomarkers Prev. 2004;13(1):125-31.
- Verkerk R, Schreiner M, Krumbein A, et al. Glucosinolates in Brassica vegetables: the influence of the food supply chain on intake, bioavailability and human health. Mol Nutr Food Res. 2009 Sep;53 Suppl 2:S219.
- Beklemisheva AA, Feng J, Yeh YA, Wang LG, Chiao JW. Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate via Sp1 and androgen receptor down-regulation. Prostate. 2007 Jun 1;67(8):863-70.
- Smith S, Sepkovic D, Bradlow HL, Auborn KJ. 3,3’-Diindolylmethane and genistein decrease the adverse effects of estrogen in LNCaP and PC-3 prostate cancer cells. J Nutr. 2008 Dec;138(12):2379-85.
- Smith S, Sepkovic D, Bradlow HL, Auborn KJ. 3,3’-Diindolylmethane and genistein decrease the adverse effects of estrogen in LNCaP and PC-3 prostate cancer cells. J Nutr. 2008 Dec;138(12):2379-85.
- Ramirez MC, Singletary K. Regulation of estrogen receptor alpha expression in human breast cancer cells by sulforaphane. J Nutr Biochem. 2009 Mar;20(3):195-201.
- Marconett CN, Sundar SN, Tseng M, et al. Indole-3-carbinol downregulation of telomerase gene expression requires the inhibition of estrogen receptor-alpha and Sp1 transcription factor interactions within the hTERT promoter and mediates the G1 cell cycle arrest of human breast cancer cells. Carcinogenesis. 2011 Sep;32(9):1315-23.
- Rajoria S, Suriano R, George A, et al. Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3’-diindolylmethane in thyroid cancer. PLoS One. 2011;6(1):e15879.
- Vivar OI, Saunier EF, Leitman DC, Firestone GL, Bjeldanes LF. Selective activation of estrogen receptor-beta target genes by 3,3’-diindolylmethane. Endocrinology. 2010 Apr;151(4):1662-7.
- Marconett CN, Singhal AK, Sundar SN, Firestone GL. Indole-3-carbinol disrupts estrogen receptor-alpha dependent expression of insulin-like growth factor-1 receptor and insulin receptor substrate-1 and proliferation of human breast cancer cells. Mol Cell Endocrinol. 2012 Nov 5;363(1-2):74-84.
- Budhraja A, Gao N, Zhang Z, et al. Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo. Mol Cancer Ther. 2012 Jan;11(1):132-42.
- He J, Xu Q, Wang M, et al. Oral Administration of apigenin inhibits metastasis through AKT/P70S6K1/MMP-9 pathway in orthotopic ovarian tumor model. Int J Mol Sci. 2012;13(6):7271-82.
- King JC, Lu QY, Li G, et al. Evidence for activation of mutated p53 by apigenin in human pancreatic cancer. Biochim Biophys Acta. 2012 Feb;1823(2):593-604.
- Mafuvadze B, Liang Y, Besch-Williford C, Zhang X, Hyder SM. Apigenin induces apoptosis and blocks growth of medroxyprogesterone acetate-dependent BT-474 xenograft tumors. Horm Cancer. 2012 Aug;3(4):160-71.
- Hoensch H, Groh B, Edler L, Kirch W. Prospective cohort comparison of flavonoid treatment in patients with resected colorectal cancer to prevent recurrence. World J Gastroenterol. 2008 Apr 14;14(14):2187-93.
- Silvan S, Manoharan S, Baskaran N, Anusuya C, Karthikeyan S, Prabhakar MM. Chemopreventive potential of apigenin in 7,12-dimethylbenz(a)anthracene induced experimental oral carcinogenesis. Eur J Pharmacol. 2011 Nov 30;670(2-3):571-7.
- Byun S, Park J, Lee E, et al. Src kinase is a direct target of apigenin against UVB-induced skin inflammation. Carcinogenesis. 2012 Nov 17.
- Gomez-Garcia F, Lopez-Jornet M, Alvarez-Sanchez N, Castillo-Sanchez J, Benavente-Garcia O, Vicente Ortega V. Effect of the phenolic compounds apigenin and carnosic acid on oral carcinogenesis in hamster induced by DMBA. Oral Dis. 2012 Jul 16.
- Bacher N, Tiefenthaler M, Sturm S, et al. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells. Br J Haematol. 2006 Mar;132(5):615-22.
- Rinner B, Li ZX, Haas H, et al. Antiproliferative and pro-apoptotic effects of Uncaria tomentosa in human medullary thyroid carcinoma cells. Anticancer Res. 2009 Nov;29(11):4519-28.
- Pilarski R, Filip B, Wietrzyk J, Kuras M, Gulewicz K. Anticancer activity of the Uncaria tomentosa (Willd.) DC. preparations with different oxindole alkaloid composition. Phytomedicine. 2010 Dec 1;17(14):1133-9.
- Emanuel P, Scheinfeld N. A review of DNA repair and possible DNA-repair adjuvants and selected natural anti-oxidants. Dermatol Online J. 2007;13(3):10.
- Anter J, Romero-Jimenez M, Fernandez-Bedmar Z, et al. Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol, and protocatechuic acid. J Med Food. 2011 Mar;14(3):276-83.
- Farias I, do Carmo Araujo M, Zimmermann ES, et al. Uncaria tomentosa stimulates the proliferation of myeloid progenitor cells. J Ethnopharmacol. 2011 Sep 1;137(1):856-63.
- Santos Araújo Mdo C, Farias IL, Gutierres J, et al. Uncaria tomentosa-adjuvant treatment for breast cancer: Clinical trial. Evid Based Complement Alternat Med. 2012;2012:676984.
- Cheng AC, Jian CB, Huang YT, Lai CS, Hsu PC, Pan MH. Induction of apoptosis by Uncaria tomentosa through reactive oxygen species production, cytochrome c release, and caspases activation in human leukemia cells. Food Chem Toxicol. 2007 Nov;45(11):2206-18.
- Huang SC, Ho CT, Lin-Shiau SY, Lin JK. Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun. Biochem Pharmacol. 2005 Jan 15;69(2):221-32.
- Moran AE, Carothers AM, Weyant MJ, Redston M, Bertagnolli MM. Carnosol inhibits beta-catenin tyrosine phosphorylation and prevents adenoma formation in the C57BL/6J/Min/+ (Min/+) mouse. Cancer Res. 2005 Feb 1;65(3):1097-104.
- Sancheti G, Goyal PK. Effect of Rosmarinus officinalis in modulating 7,12-dimethylbenz(a)anthracene induced skin tumorigenesis in mice. Phytother Res. 2006 Nov;20(11):981-6.
- Ngo SN, Williams DB, Head RJ. Rosemary and cancer prevention: preclinical perspectives. Crit Rev Food Sci Nutr. 2011 Dec;51(10):946-54.
- Valdes A, Garcia-Canas V, Rocamora-Reverte L, Gomez-Martinez A, Ferragut JA, Cifuentes A. Effect of rosemary polyphenols on human colon cancer cells: transcriptomic profiling and functional enrichment analysis. Genes Nutr. 2012 Aug 25.
- Tai J, Cheung S, Wu M, Hasman D. Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro. Phytomedicine. 2012 Mar 15;19(5):436-43.
- Shabtay A, Sharabani H, Barvish Z, et al. Synergistic antileukemic activity of carnosic acid-rich rosemary extract and the 19-nor Gemini vitamin D analogue in a mouse model of systemic acute myeloid leukemia. Oncology. 2008;75(3-4):203-14.
- Singletary KW, Rokusek JT. Tissue-specific enhancement of xenobiotic detoxification enzymes in mice by dietary rosemary extract. Plant Foods Hum Nutr. 1997;50(1):47-53.
- Tsai CW, Lin CY, Wang YJ. Carnosic acid induces the NAD(P)H: quinone oxidoreductase 1 expression in rat clone 9 cells through the p38/nuclear factor erythroid-2 related factor 2 pathway. J Nutr. 2011 Dec;141(12):2119-25.
- Jindal A, Soyal D, Sancheti G, Goyal PK. Radioprotective potential of Rosemarinus officinalis against lethal effects of gamma radiation : a preliminary study. J Environ Pathol Toxicol Oncol. 2006;25(4):633-42.
- Sancheti G, Goyal PK. Prevention of radiation induced hematological alterations by medicinal plant Rosmarinus officinalis, in mice. Afr J Tradit Complement Altern Med. 2006;4(2):165-72.
- Soyal D, Jindal A, Singh I, Goyal PK. Modulation of radiation-induced biochemical alterations in mice by rosemary (Rosemarinus officinalis) extract. Phytomedicine. 2007 Oct;14(10):701-5.
- Jindal A, Agrawal A, Goyal PK. Influence of Rosemarinus officinalis extract on radiation-induced intestinal injury in mice. J Environ Pathol Toxicol Oncol. 2010;29(3):169-79.
- Slamenova D, Kuboskova K, Horvathova E, Robichova S. Rosemary-stimulated reduction of DNA strand breaks and FPG-sensitive sites in mammalian cells treated with H2O2 or visible light-excited Methylene Blue. Cancer Lett. 2002 Mar 28;177(2):145-53.
- Kar S, Palit S, Ball WB, Das PK. Carnosic acid modulates Akt/IKK/NF-kB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis. 2012 Jul;17(7):735-47.
- Yesil-Celiktas O, Sevimli C, Bedir E, Vardar-Sukan F. Inhibitory effects of rosemary extracts, carnosic acid and rosmarinic acid on the growth of various human cancer cell lines. Plant Foods Hum Nutr. 2010 Jun;65(2):158-63.
- Sharabani H, Izumchenko E, Wang Q, et al. Cooperative antitumor effects of vitamin D3 derivatives and rosemary preparations in a mouse model of myeloid leukemia. Int J Cancer. 2006 Jun 15;118(12):3012-21.