Cancer chemoprevention apoptosis

Izzotti, R. A. Lubet, G. J. Kelloff, and S. De Flora. Modulation of apoptosis by cigarette smoke and cancer chemopreventive agents in the respiratory tract of rats. Carcinogenesis 2001 22(3) 375-380. 

Milk fat contains small amounts of ether lipids. Synthetic ether lipids at low concentrations are potent anti-neoplastic agents. Cell culture studies showed that they inhibited cell growth, induced differentiation, promoted apoptosis and showed anti-metastatic activity. In human chemoprevention trials ether lipids have been administered parenterally. Although the ether bond is preserved when these lipids are delivered orally, no cancer chemoprevention studies have utilized dietary ether lipids (Parodi, 2004). 

Fesus L, Szondy Z, Uray I. Probing the molecular program of apoptosis by cancer chemopreventive agents. J Cell Biochem 1995 22(Suppl) 151-61. 

Cell cycle arrest, apoptosis, cell proliferation, and cell differentiation are all mediated through signal transduction processes and appeared to be important executive targets for the operation of cancer chemoprevention. Several transducer proteins, such as cdks, cyclins, cdk inhibitors, ROS, cytochrome c, caspases, PARR Bcl-2, Bax, p53, c-jun, c-fos, c-myc, PKC, PKB, PI3K, MARK, NFkB, IKK, etc. are involved in these important cellular functions. Effects of the above mentioned phytopolyphenols on the activities of these transducer proteins were investigated by our laboratory and others, and the results will be selectively described and discussed. 

Recently garcinol (46), also called camboginol, has attracted considerable interest because of its associated beneficial health properties, including antiulcer activity [59], anti-glycation activity [60], cancer chemopreventive activity against colonic aberrant crypt foci (ACF) in an animal model [63], induction of apoptosis through cytochrome c release and activation of caspases in human leukemia cells [61]. It also showed strong antioxidant activity [59,60]. 

The compounds from the ethyl acetate fraction showing strong apoptosis-inducing activity were identified by spectral methods as epidioxysterols. The in vitro results suggest that induction of apoptosis by epidioxysterols may provide a pivotal mechanism for its cancer chemoprevention. 

Samaha HS, Kelloff GJ, Steele V, Rao CV, Reddy BS. Modulation of apoptosis by sulindac, curcumin, phenylethyL3-methylcaffeate, and 6-phenylhexyl isothiocyanate apoptotic index as a biomarker in colon cancer chemoprevention and promotion. Cancer Res 1997 57 1301-1305. 

Chan, T.A, Nonsteroidal anti-inflammatory drags, apoptosis, and colon-cancer chemoprevention. Lancer Omco/., 3,166-174,2002. 

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