Anti-apoptotic mechanism

Li J, Zhang X, Zhang J. Study of the anti-apoptotic mechanism of ginsenoside Rgl in cultured neurons. Acta Pharmacol Sin 1997 32 4064-10. 

A.K. Jonassen, B.K. bar, O.D. Mjos, M.N. Sack, D.S. Latchman and D.M. Yellon, Insulin administered at reoxygenation exerts a cardioprotective effect in myocytes by a possible anti-apoptotic mechanism, J. Moll. Cel. Cardiol. 32(5), 757-764 (2000). 

Azad, N., Vallyathan, V., Wang, L., Tantishaiyakul, V., Stehlik. C.. Leonard. S.S.. and Rojanasakul. Y. (2006). S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation a novel anti-apoptotic mechanism that suppresses apoptosis. J. Biol. Chem. 281, 34124-34134. 

Andrabi, S. A., Sayeed, I., Siemen, D., Wolf, G. Horn, T. F. (2004). Direct inhibition of the mitochondrial permeability transition pore a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J. 18, 869-71. 

There are several hypotheses for a specific mechanism by which ONOO- can control the open state of the PTPC. Briefly the PTPC is regulated by primary constituents of the pore, including the inner membrane adenine nucleotide translocase (ANT) and the outer membrane protein voltage-dependent anion channel (VDAC or porin). The VDAC-ANT complex can bind to signaling proteins that modulate permeability transition, such as pro-apoptotic Bax (which opens the pore) and anti-apoptotic Bcl-2... 

The mechanistic basis of the anti-neoplastic activity of UDCA and the explanation for the significant difference in bioactivity of UDCA compared with DCA despite marked similarity in chemical structure remain unresolved. UDCA administration in healthy volunteers and colorectal adenoma patients has been demonstrated to decrease the proportion of DCA in aqueous phase stool. Therefore, one possible mechanism of the chemopreventative activity of UDCA is reduction of mucosal secondary bile acid exposure. Consistent with this idea, UDCA administration has been demonstrated to reduce the incidence of K-ras mutations and decrease Cox-2 expression in AOM-induced tumors, which is the opposite of the reported effects of DCA in the same model. However, it is clear that exogenous administration of UDCA has direct anti-neoplastic activity on human CRC cells in vitro, either alone or in combination with DCA, including anti-proliferative and anti-apoptotic effects, as well as induction of cell senescence. " ... 

The mechanism by which cisplatin kills a cell represents a complex story. This review has identified numerous determinants of cellular response to cisplatin. DNA platination is an essential first step in the eventual demise of a cell, but the final outcome is also dependent upon the capacity for DNA repair, the ability to arrest cell cycle progression, the p53 status, the activity of intracellular protein kinase cascades, and the expression levels of pro-and anti-apoptotic members of the Bcl-2 family. It is likely that many other determinants remain to be identified. Many investigators are trying to predict the response of a tumor based on one or several of these parameters, but the above discussion would suggest it may be difficult if not impossible to predict sensitivity of a tumor to cisplatin without directly measuring it. 

In the case of diterpenes, a different mechanism may be involved in antiinflammatory activity. Interference with DNA-binding activity of p50 protein of NF-kB factor seems to be a mechanism, as shown with kamebakaurin, a kaurane diterpene. This compound did not prevent degradation of ItcB-a isoform or nuclear translocation of NF-kB factor, and the covalent modification of cysteine 62 of p50 by kamebakaurin was proven. Prevention of the induced expression of anti-apoptotic genes and an increase in the induced caspase 8 activity were also observed. These... 

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