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Biotech / Medical : Biotech Valuation -- Ignore unavailable to you. Want to Upgrade?

To: Elmer who wrote (7421)	12/5/2002 9:30:31 AM
From: Sam Citron	Respond to of 52153

Even if nicotine were just the hook for another substance in the cigarette that causes cancer, as you postulate, then nicotine would still be an indirect cause of cancer. It's not my field, however, so I prefer not to speculate.

To: Elmer who wrote (7421)	12/5/2002 11:27:05 AM
From: Biomaven	Read Replies (2) \| Respond to of 52153

OT Has it been proved that nicotine causes cancer? Not to my knowledge (other than indirectly, of course). There is some evidence (see abstract below) that nicotine may inhibit apoptosis (cell suicide), and this might exacerbate or help initiate cancer or make chemotherapy less effective. Nicotine's effects are complex, though - it also has effects on the heart and the pancreas, for example, in addition to its well known effects on the brain. J Biol Chem 2002 Nov 5; [epub ahead of print] Related Articles,Links A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis. Mai H, May WS, Gao F, Jin Z, Deng X. Department of Medicine, University of Florida, Gainesville, FL 32610-0232. Nicotine is not only a major component in tobacco but also a survival agonist that inhibits apoptosis induced by diverse stimuli including chemotherapeutic drugs. However, the intracellular mechanism(s) involved in nicotine suppression of apoptosis is unclear. Bcl2 is a potent antiapoptotic protein and tumor promotor that is expressed in both small-cell (SCLC) and non-small-cell lung cancer (NSCLC) cells. It is possible that nicotine may regulate Bcl2 to stimulate cell survival. Here we report that nicotine can induce Bcl2 phosphorylation exclusively at the serine70 site in association with prolonged survival of SCLC H82 cells expressing wild-type but not the phosphorylation deficient S70A mutant Bcl2 following treatment with chemotherapeutic agents (i.e. cisplatin or VP-16). Nicotine induces activation of PKCa and the MAPKs ERK1/2 that are physiological Bcl2 kinases. Furthermore, ET-18-OCH3, a specific phospholipase C (PLC) inhibitor, blocks nicotine-stimulated Bcl2 phosphorylation and promotes apoptosis, suggesting that PLC may be involved in nicotine activation of Bcl2 kinases. Using a genetic approach, the gain-of-function S70E mutant, which mimics ser70 site phosphorylation in the flexible loop domain, potently enhance chemoresistance in SCLC cells. Thus, nicotine-induced cell survival results, at least in part, from a mechanism that involves Bcl2 phosphorylation. Therefore, novel therapeutic strategies for lung cancer expressing Bcl2 may be used to abrogate Bcl2's anti-apoptotic activity by inhibiting multiple upstream nicotine-activated pathways. Peter