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Researchers Discover Garlic's Ability To Reduce Colon Cancer Risk Factors
Investigators find more evidence that aged garlic extract 
may significantly benefit those at risk of colon cancer

A new study completed through collaborative efforts by researcher's at Columbia University and the Institute for Cancer Prevention found that an ingredient in Kyolic® Aged Garlic Extract (AGE) helps stop growth of colon cancer cells. The results were published in the October issue of Cancer Research.

Dr. John Thomas Pinto, a leading cancer researcher at the Institute of Cancer Prevention, in Valhalla, New York and Dr. Danhua Xiao at the Herbert Irving Comprehensive Cancer Center of Columbia University have found that S-allylmercaptocysteine (SAMC), a water-soluble sulfur compound present in AGE, stops colon cancer cells from dividing. It prevents the formation of small filaments, known as microtubule spindles, that help separate newly formed cells into two new daughter cells. SAMC seems to exert its antigrowth effect by reacting directly with the proteins that form the structure of the spindles and disrupting their assembly. This process stops cancer cells before they can divide, and subsequently triggers other proteins within the cell that cause the cancer cell to undergo programmed cell death. This is the first time garlic-derived compounds have been shown to exert their effect by acting directly with specific cell proteins and modifying their function.

"These results can have an important impact on public health, " said Dr. Pinto. "This work demonstrates that individual allium-derived compounds present also in aged garlic extract (AGE) may act by slowing the rate of progression of established colon cancer cells. Because of its content of SAMC, the study suggests that AGE may also be a useful and beneficial dietary addition for people at risk." 

Evidence of garlic's anticarcinogenic role comes from both epidemiologic and laboratory investigations. Case control epidemiological studies in northeast China (You et al., 1988) and Italy (Buiatti et al., 1989) showed that there are strong reverse trends in stomach cancer risk with dietary intake of garlic. Similarly, a lower risk of colon cancer for American consumers of garlic was reported in the Iowa Women's Health Study published in 1994 (Steinmetz et al.). Although the minimum daily intake of garlic required to reduce cancer risk remains to be determined, garlic had been categorized as a dietary anticarcinogen worthy of further investigation.

Numerous other laboratory studies have reported beneficial effects of garlic. Specifically, AGE and its constituents have demonstrated anti-cancer effects in many cancer models including bladder tumors, melanoma cells, neuroblastoma cells, skin cancer, breast cancer, colon cancer, prostate cancer, esophageal cancer, stomach and lung cancer and erythroleukemia.

More than 350 scientific studies have been completed using AGE. These studies, performed at major universities and research institutes, have focused on various aspects of garlic's health benefits including cholesterol and high blood pressure lowering effects, homocysteine control, inhibition of LDL oxidation, decreasing platelet aggregation and adhesion thus preventing blood cells from clotting too soon, stimulating blood circulation by widening blood vessels, controlling immune response, improving cognitive effects through increasing blood flow to the brain, improving liver function and anti-tumor effects. 

Kyolic® is a trademark and a product of Wakunaga of America Company, a subsidiary of Wakunaga Pharmaceutical Company. 

Biography -- John Thomas Pinto, Ph.D.

Dr. John Thomas Pinto is Senior Scientist at the Institute for Cancer Prevention (IFCP) (formerly the American Health Foundation) in Valhalla, New York and an Adjunct Professor of Medicine at New York Medical College. Since 1980, Dr. Pinto has served as the Associate Program Director of the Clinical Nutrition Research Unit (CNRU) that was granted by the National Cancer Institute at the NIH to provide nutrition education and training in cancer research at the Institute for Cancer Prevention and its collaborating institutions, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, Strang Cancer Prevention Center, and the Rockefeller University. As Director of the Nutrition Research Laboratory at IFCP, his research interests have focused upon developing chemopreventive strategies for diminishing risk of developing primary and secondary colon and prostate cancers. In particular, his research has centered on the effects of specific phytonutrients upon oxidative and reductive metabolic pathways within human colon and prostate cancer cells and is interested in characterizing mechanisms by which plant-derived constituents regulate cell growth and metabolism by modifying signal transduction pathways through sulfhydryl-disulfide regulation of proteins.

October 15, 2003 issue of 

Cancer Research

Induction of Apoptosis by the Garlic-Derived Compound S-Allylmercaptocysteine (SAMC) Is Associated with Microtubule Depolymerization and c-Jun NH2-Terminal Kinase 1 Activation1 
Danhua Xiao, John T. Pinto, Jae-Won Soh, Atsuko Deguchi, Gregg G. Gundersen, Alexander F. Palazzo, Jung-Taek Yoon, Haim Shirin and I. Bernard Weinstein2  Institute of Human Nutrition [D. X.], Herbert Irving Comprehensive Cancer Center [J-W. S., A. D., J-T. Y., I. B. W.], Department of Anatomy and Cell Biology [G. G. G., A. F. P.], College of Physicians and Surgeons, Columbia University, New York, New York 10032; American Health Foundation, Valhalla, New York 10595 [J. T. P.]; and E. Wolfson Medical Center, Holon, 58100 Israel [H. S.] 

Epidemiological and experimental carcinogenesis studies provide evidence that components of garlic (Allium sativum) have anticancer activity. We recently reported that the garlic derivative S-allylmercaptocysteine (SAMC) inhibits growth, arrests cells in G2-M, and induces apoptosis in human colon cancer cells (Shirin et al., Cancer Res., 61: 725-731, 2001). Because a fraction of the SAMC-treated cells are specifically arrested in mitosis, we examined the mechanism of this effect in the present study. Immunofluorescent microscopy revealed that the treatment of SW480 cells or NIH3T3 fibroblasts with 150 ƒÊM SAMC (the IC50 concentration) caused rapid microtubule (MT) depolymerization, MT cytoskeleton disruption, centrosome fragmentation and Golgi dispersion in interphase cells. It also induced the formation of monopolar and multipolar spindles in mitotic cells. In vitro turbidity assays indicated that SAMC acted directly on tubulin to cause MT depolymerization, apparently because it interacts with -SH groups on tubulin. To investigate the signaling pathways involved in SAMC-induced apoptosis, we assayed c-Jun NH2-terminal kinase (JNK) activity and found that treatment with SAMC caused a rapid and sustained induction of JNK activity. The selective JNK inhibitor SP600125 inhibited the early phase (24 h) but not the late phase (48 h and later) of apoptosis induced by SAMC. Expression of a dominant-negative mutant of JNK1 in SW480 cells inhibited apoptosis induced by SAMC at 24 h but had no protective effect at 48 h. JNK1-/- mouse embryonic fibroblasts were resistant to SAMC-induced apoptosis at 24 h but not at 48 h. On the other hand, the inhibition or abrogation of JNK1 activity did not inhibit the G2-M arrest induced by SAMC. SAMC also activated caspase-3. The general caspase inhibitor z-VAD-fmk inhibited both early and late phases of apoptosis induced by SAMC. We conclude that the garlic-derived compound SAMC exerts antiproliferative effects by binding directly to tubulin and disrupting the MT assembly, thus arresting cells in mitosis and triggering JNK1 and caspase-3 signaling pathways that lead to apoptosis.

Supporting Research

Previous studies on AGE and SAMC for a Healthy Colon
Dr. John Milner and his group at Pennsylvania State University found that SAMC is effective at suppressing the growth of cultured human colon tumor cells. Three hundred micro gram of SAMC caused a 23% suppression in cell growth. Many factors are involved in the development and progression of colon. However, continuous intake of AGE may provide beneficial compounds the colon can use as ammunition against abnormal cell growth.

S-allylmercaptocysteine (SAMC) Confirmed to be Present Only in Kyolic/ Aged Garlic Extract
S-allylmercaptocysteine (SAMC) is a sulfur compound naturally generated during the aging process. Fresh garlic cloves contain no SAMC. However, the aging process causes this compound to increase significantly.

SAMC Inhibited the Growth of Breast and Prostate Cancer Cells
Dr. Steiner at East Carolina University recently found that it could inhibit the growth of two hormone responsive human breast and prostate cancer cell lines. This research is relevant because hormones naturally produced in the body can enhance the growth of these human cancer cells so finding safe compounds that inhibit their growth may be helpful. This research is in agreement with the former work of Dr. Pinto while at Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University, who also found that SAMC may inhibit the growth of human prostate cancer cells. The cells used in their study were androgen responsive prostate cancer cells. Testosterone, the principal male hormone, enhances the activity/growth of prostate cancer cell. SAMC was found to enhance the catabolism or degradation of testosterone. Therefore, the researchers suggested that SAMC, by catabolizing testosterone, hampered the progression or activation of these prostate cancer cells. Prostate specific antigen (PSA) levels were also markedly reduced after treatment with SAMC. PSA is considered as a marker for prostate cancer.

SAMC increased reduced glutathione (a detoxification tripeptide) in prostate cancer cells. The reduced form of glutathione may hinder cancer cell growth by regulating activity of enzymes within cancer cells, such as ornithine decarboxylase, that may influence the cells rate of growth. SAMC may also directly inhibit ornithine decarboxylase. 

SAMC shown to be beneficial in various studies
SAMC has demonstrated an array of effects in studies. Specifically, it has shown antioxidative effects, liver protective effects, and anti-cancer effects in studies including colon, prostate and breast cancer. Kyolic/Aged Garlic Extract, which naturally contains SAMC has been shown to be safe and its intake may be a prudent addition to a healthy diet and lifestyle.

According to Dr. Richard Rivlin, Cornell University's director of clinical nutrition, these cultured human cells also produce compounds characteristic of human tumors, making them a good model of human disease. Specifically, prostate specific antigen (PSA) is released from these cancer cells when they are growing and is used as a marker of cancer progression in men. PSA itself can also promote cancer cell proliferation. Treatment with SAMC also markedly reduced PSA levels.

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