Brocco SGS: Cancer Prevention and Liver

SGS Sulforaphane Glucosinolate: Phase 2 Liver Enzymes, Chemo-Protective Effects and Liver Detoxification

By Geoff D’Arcy, Lic. Ac., D.O.M

Previously published in the Wellbeing Journal

 

There is compelling scientific evidence that consumption of vegetables and fruits helps to reduce the risk of some cancers. The USDA’s Dietary Guidelines for Americans, as well as the National Research Council and American Institute of Cancer Research recommendations, all reflect this growing knowledge. It is estimated that 10.3 million new cancer cases are diagnosed each year worldwide, making cancer prevention a major public health priority. Those simple words from your mother held much truth. Vegetables do keep us healthy, and can be a powerful weapon against cancer. According to a recent international expert report, dietary changes can prevent 30 to 40 percent of cancer cases, (three to four million cases annually).

 

What is it about vegetables that produce those healthy effects? It’s the naturally protective phytochemicals from thousands of naturally occurring chemicals in vegetables. The ‘stars’of these anti cancer chemicals in the body are: Allicin, found in garlic; Carotenoids, found in carrots; Lycopene, in tomatoes; and another amazing compound found in broccoli, Sulforaphane glucosinolate (SGS ). These compounds increase the body’s own defense system against carcinogens. Cells in the body contain a family of detoxification enzymes (Phase 2 enzymes) that neutralize cancer-causing chemicals as well as free radicals before they damage DNA and initiate cancer. Chemo-protection can be accomplished by activating the body’s Phase 2 "defense" The Phase Two enzymes are an integral part of the body’s amazing detoxification system, neutralizing carcinogens and making them inactive. This detoxification system turns carcinogens and other toxic substances into harmless molecules that are excreted from the body.

 

In his article "Sulforaphane Stimulates the Body’s Cancer Fighting Enzymes," Richard Conant describes how sulforaphane works. “The detoxification of carcinogens and other toxic substances takes place in the liver, and involves two distinct enzyme driven processes or "phases." Phase One enzymes neutralize toxins by various routes. Some of these convert toxins into substances that are immediately eliminated. However, other Phase One steps convert toxins into intermediate products which are carcinogenic themselves, and require further treatment before they can be excreted. Phase Two enzymes do this vital job. Phase Two enzymes deactivate these carcinogenic metabolites of Phase One, and the final breakdown product is then eliminated once and for all. [For an excellent review of this subject, see Encyclopedia of Natural Medicine, by Drs. Michael Murray and Joseph Pizzo]. Phase Two is critical. If Phase One is in good working order, but Phase Two is not, the potential threat from carcinogens increases. It is vitally important to keep Phase Two operating well. This is where sulforaphane plays its cancer preventive role. Sulforaphane is a powerful inducer of Phase 2 enzymes.”

 

According to studies by Dr. Paul Talalay and his colleagues at Johns Hopkins University School of Medicine, sulforaphane enhances the cancer-protective capacity of animal cells. Sulforaphane in Brocolli sprouts induces Phase 2 (detoxification) enzymes, which are the enzymes that help to deactivate carcinogens and free radicals, thereby enhancing the liver and body’s own defense system against cancer-causing chemicals.

 

Some of the best growing techniques now guarantee large quantities, up to 5,500 parts per million, of sulforaphane within organically grown broccoli sprout powder. "Three-day-old broccoli sprouts consistently contain 20 to 50 times the amount of chemo-protective compounds found in mature broccoli heads, and may offer a simple, dietary means of chemically reducing cancer risk," says Paul Talalay, M.D. (See Fahey, Zhang and Talalay, " Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens.") In general, Brassica family plants such as broccoli are rich in sulforaphane in its glucosinolate precursor form. Unfortunately, broccoli must be eaten in large quantities to substantially reduce the risk of cancer. Preliminary studies suggest that to cut the risk of cancer in half, the average person would need to eat about two pounds of broccoli or similar vegetables per week. Because of the Johns Hopkins research they were able to identify that broccoli varies in sulforaphane content, and that certain varieties of young broccoli sprouts, grown under standardized conditions, contain large, uniform quantities of the compound. And since the concentration of sulforaphane is much higher in broccoli sprouts than in mature broccoli, the same reduction in risk theoretically might be had with a weekly intake of just over an ounce of sprouts, and maybe a few capsules of sprout powder.

 

In animal studies, sulforaphane blocked tumor development, reducing incidence, multiplicity, and size of carcinogen-induced mammary tumors. Small quantities of broccoli sprout extracts have reduced the incidence and size of mammary tumors in animals. Talalay’s research team fed extracts of the sprouts to groups of 20 female rats for five days, and exposed them and a control group that had not received the extracts to a carcinogen, dimethylbenzanthracene. The rats that received the extracts developed fewer tumors, and those that did get tumors had smaller growths that took longer to develop. The number of rats that developed tumors was reduced by as much as 60%, the number of tumors in each animal was reduced by 80%, and the size of the tumors that did develop was reduced by 75%. Furthermore, the tumors’ appearance was delayed and they grew more slowly. Clinical studies are underway to further explore the effects of broccoli sprouts on protective biomarkers against human cancer.

 

Scientists at the American Health Foundation discovered that sulforaphane inhibited the formation of pre-malignant lesions in the colons of rats, and researchers in France found that sulforaphane induced cell death in human colon carcinoma cells. This study suggests that "in addition to the activation of detoxifying enzymes, induction of apoptosis [cell death] is also involved in the sulforaphane-associated chemo-prevention of cancer." These results have not yet been validated in humans, but are making a lot of scientists sit up and take note.

 

When to consider supplementation?

 

  • Any animal dealing with cancer presently or in the past, or anyone wanting to be sure of chemo-prevention
  • Those with liver disease to help the liver’s detoxification process
  • Dieting and releasing toxins back into the system from fat cells
  • Those wanting to reinforce detoxification

 

Some references of Broccoli Sprout research:

 

Dinkova-Kostova, A.T., Abeygunawardana, C., and Talalay, P. (1998) Chemoprotective Properties of Phenylpropenoids, Bis(benzylidene)cycloalkanones, and Related Michael Reaction Acceptors: Correlation of Potencies as Phase 2 Enzyme Induers and Radical Savengers. J. Med. Chem. 41, 5278-5296.

Dinkova-Kostova, A. T. and Talalay, P. (1999) Relation of Struture of Curcumin Analogs to their Potencies as Inducers of Phase 2 Detoxication Enzymes. Carcinogenesis 20, 911-914.

Talalay P. (1999) The War Against Cancer: New Hope. Proc. Amer. Philos. Soc. 143, 52-72.

Foster, C.E., Bianchet, M. A., Talalay, P., Zhao, Q., and Amzel, L.M. (1999) Crystal Structure of Human Quinone Reductase Type 2, a Metalloflavoprotein. Biochemistry 38, 9881-9886.

Fahey, J.W. and Talalay, P. (1999) Antioxidant Functions of Sulforaphane: A Potent Inducer of Phase II Detoxication Enzymes. Food Chem. Toxicol. 37, 973-979.

Steinmetz, K.A. Potter, J.D. Vegetables, fruit, and cancer prevention: A review. J Am Diet Assoc. 1996;96:1027?1039.

Fahey, J.W., Zhang, Y., Talalay, P. Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc. Natl. Acad. Sci. 1997; 94:10367?10372.

Verhoeven, D.T.H., et. al. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiology, Biomarkers & Prevention 1996;5:733?48.

Murray, M. Pizzorno, J. Encyclopedia of Natural Medicine. Rocklin, CA: Prima Publishing;1998:110?120.

Zhang, Y. Talalay, P, Cho, C., Posner, G.H. A major inducer of anti-carcinogenic protective enzymes from broccoli: Isolation and elucidation of structure. Proc. Natl. Acad. Sci. 1992;89:2399?2403.

Gerhäuser, C. et. al. Cancer chemo-preventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug metabolizing enzymes. Cancer Research 1997;57:272?78.

McDanell, R., McLean, A.E.M., Hanley, A.B., Heaney, R.K., Fenwick, G.R. Chemical and biological properties of indole glucosinolates (glucobrassicins): A review. Fd. Chem. Toxic. 1988;26(1):59?70.

Talalay, P. Mechanisms of induction of enzymes that protect against chemical carcinogenesis. in Advances in Enzyme Regulation, Vol. 28, Weber, G., Ed., 1989: Pergamon Press.

Prochaska, H.J. Santamaria, A.B., Talalay, P. Rapid detection of enzymes that protect against carcinogens. Proc. Natl. Acad. Sci. 1992;89:2394?98.

 

Here are a few of the papers and publications pertinent to broccoli sprouts, SGS, phase 2 enzymes and chemo-protective effects. They are sorted by date of publication and taken from www.brassica.com a source of live sprouts to be included in diet.

Powerful and prolonged protection of human retinal pigment epithelial cells, keratinocytes, and mouse leukemia cells against oxidative damage: the indirect antioxidant effects of sulforaphane. http://www.pnas.org/cgi/doi/10.1073/pnas.261572998 Proc. Natl. Acad. Sci. USA, Vol. 98, Issue 26, pp. 15221-15226, December 18, 2001 Xiangqun Gao, Albena T. Dinkova-Kostova, and Paul Talalay

The impaired glutathione system and its up-regulation by sulforaphane in vascular smooth muscle cells from spontaneously hypertensive rats. http://www.jhypertension.com/article.asp?ISSN=0263-6352&VOL=19&ISS=10&PAGE=1819 Hypertension, Vol. 19, pp. 1819-1825, 2001. Lingyun Wu; Bernhard H. J. Juurlink

Potent induction of Phase 2 enzymes in human prostate cells by sulforaphane. http://cebp.aacrjournals.org/cgi/content/abstract/10/9/949 Cancer Epidemiology, Biomarkers & Prevention, Vol. 10, pp. 949-954. Sept. 2001. James D. Brooks, Vincent G. Paton and Genevieve Vidanes

Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice http://www.pnas.org/cgi/content/short/98/6/3410 Proc. Natl. Acad. Sci. USA, Vol. 98, Issue 6, 3410-3415, March 13, 2001 Minerva Ramos-Gomez, Mi-Kyoung Kwak, Patrick M. Dolan, Ken Itoh, Masayuki Yamamoto, Paul Talalay, and Thomas W. Kensler JHMI Press release: Studies Show Powerful Natural Anti-Cancer System Exists: Goal Now: Fine Tune It

Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups http://www.pnas.org/cgi/content/short/98/6/3404 Proc. Natl. Acad. Sci. USA, Vol. 98, Issue 6, 3404-3409, March 13, 2001 Albena T. Dinkova-Kostova, Michael A. Massiah, Richard E. Bozak, Ronald J. Hicks, and Paul Talalay. The chemical diversity and distribution of glucosinolates and isothiocyanates among plants Phytochemistry 2001, 56:5-51. Fahey, Jed W., Zalcmann, Amy T, Talalay, Paul.

Inhibition of benzo[a]pyrene- and 1,6-dinitropyrene-DNA adduct formation in human mammary epithelial cells by dibenzoylmethane and sulforaphane. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10814878&dopt=Abstract Cancer Letters 2000 July 3; 155(1):47-54. Singletary K, MacDonald C.

Sulforaphane, A Naturally Occurring Isothiocyanate, Induces Cell Cycle Arrest and Apoptosis in HT29 Human Colon Cancer Cells http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10728709&dopt=Abstract Cancer Research 2000 March 1; 60(5):1426-1433. Gamet-Payrastre L, Li P, Lumeau S, Cassar G, Dupont MA, Chevolleau S, Gase N, Tulliez J, Terçé F.

Chemoprevention of colonic aberrant crypt foci in Fischer rats by major isothiocyanates in watercress and broccoli. Proceedings of the American Association for Cancer Research, March 2000; 41:660. Chung F-L, Conaway CC, Rao CV, Reddy BS.

Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes. http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10541453&form=6&db=m&Dopt=b Food Chem Toxicol 1999 Sep-Oct;37(9-10):973-9 Jed W. Fahey, Paul Talalay

The War Against Cancer: New Hope, Proceedings of the American Philosophical Society, March 1999, Vol. 143(1), pp. 52-72., Talalay, Paul.

Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens http://www.pnas.org/cgi/content/abstract/94/19/10367 Proc. Natl. Acad. Sci. USA, Vol. 94, pp. 10367-10372, September 16, 1997. Jed W. Fahey, Yuesheng Zhang, and Paul Talalay

Electrophile and Antioxidant Regulation of Enzymes that Detoxify Carcinogens http://www.pnas.org/cgi/content/abstract/92/19/8965 Proc Natl Acad Sci U S A 1995 Sep 12;92(19):8965-9 T Prestera and Paul Talalay

Anticarcinogenic Activities of Sulforaphane and Structurally Related Synthetic Norbornyl Isothiocyanates http://www.pnas.org/cgi/content/abstract/91/8/3147 Proc Natl Acad Sci USA 1994 Apr 12;91(8):3147-50 Y Zhang, TW Kensler, C Cho, GH Posner and P Talalay

Chemical and Molecular Regulation of Enzymes that Detoxify Carcinogens http://www.pnas.org/cgi/content/abstract/90/7/2965 Proc Natl Acad Sci USA 1993 Apr 1;90(7):2965-9 T Prestera, WD Holtzclaw, Y Zhang and P Talalay

A Major Inducer of Anticarcinogenic Protective Enzymes from Broccoli: Isolation and Elucidation of Structure http://www.pnas.org/cgi/content/abstract/89/6/2399 Proc Natl Acad Sci USA 1992 Mar 15;89(6):2399-403 Y Zhang, P Talalay, C Cho and GH Posner

Rapid Detection of Inducers of Enzymes that Protect Against Carcinogens http://www.pnas.org/cgi/content/abstract/89/6/2394 Proc Natl Acad Sci USA 1992 Mar 15;89(6):2394-8 HJ Prochaska, AB Santamaria and P Talalay

Chemoprotection against cancer by phase 2 enzyme induction. http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8597048&form=6&db=m&Dopt=b Toxicol Lett 1995 Dec;82-83:173-9 Talalay P, Fahey JW, Holtzclaw WD, Prestera T, Zhang Y