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Induction of apoptosis by SAMC, a biotransformed garlic derivative, through caspase protein activation on human gastric cancer cells
Author(s) -
Lee Yongkyu
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.315.3
Subject(s) - apoptosis , glutathione , caspase , cytochrome c , carcinogenesis , population , cancer cell , stat5 , caspase 3 , programmed cell death , xiap , biology , cancer research , microbiology and biotechnology , cancer , chemistry , signal transduction , biochemistry , medicine , enzyme , genetics , environmental health
Epidemiological and experimental carcinogenesis studies show evidence that components of garlic have anticancer activity. Most of allyl sulfides of garlic, which are absorbed in gastrointestinal tract, were also reported to biotransform to the corresponding allylmercapto glutathione S ‐congugate after reacting with endogenous antioxidants, such as cysteine and reduced glutathione(GSH). One of these allylmercapto glutathione S ‐congugate, SAMC( S ‐allylmercapto‐L‐cysteine), was reported that showed inhibitory effect on tumorigenesis, but the mechanisms of which are poorly understood. In the present study, we investigated the effect of SAMC on the growth of human gastric cancer SNU‐1 cells. Upon treatment with SAMC, a concentration‐dependent inhibition of cell proliferation was observed and cells developed many of the hall mark features of apoptosis, including DNA fragmentation and an increase in the sub‐diploid population. Also we investigated the effect of SAMC on the mitochondria release of cytochrome c, which is known that enters the cytosol and forms a complex with Apaf‐1 and a pro‐form of caspase‐9, then induces the activation of other signaling proteins. The anti‐proliferative and apoptotic effect of SAMC was associated with an induction of Bax, p53, and caspase‐9, rather than an induction of Bcl‐2 and p21. Mitochondrial cytochrome c activation and an in vitro caspase‐3 activity assay demonstrated that the activation of caspases accompanies the apoptotic effect of SAMC, which mediates cell death. These results suggest that the apoptotic effect of SAMC on gastric cancer SNU‐1 cells may converge caspase‐3 activation through the induction of Bax and p53, rather then Bcl‐2 and p21.