Apoptosis inducers

HBV, hepatitis B HCV, hepatitis C IAP, inhibitor of apoptosis protein DBM, IAP binding motifs INCA, inhibitory CARD NASH, non-alcoholic steatohepatitis PCD, programmed cell death PCI, pan-caspase inhibitor OA, osteoarthritis RA, rheumatoid arthritis Smac, second mitochondria-derived activator of caspases TRAIL, tumor necrosis factor-related apoptosis-inducing ligand. 

Mitochondrial permeability transition involves the opening of a larger channel in the inner mitochondrial membrane leading to free radical generation, release of calcium into the cytosol and caspase activation. These alterations in mitochondrial permeability lead eventually to disruption of the respiratory chain and dqDletion of ATP. This in turn leads to release of soluble intramito-chondrial membrane proteins such as cytochrome C and apoptosis-inducing factor, which results in apoptosis. 

CHEN Y R, WANG w, KONG A N and TAN T H (1998) Molecular mechanisms of c-Jim N-terminal kinase-mediated apoptosis induced by anticarcinogenic isothiocyanates , J Biol Chem, 273 1769-75. 

Sandur, S.K. et ah, Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) suppresses NF-kappa B activation and NF-kappa B-regulated gene products through modulation of p65 and I-kappa-B-alpha kinase activation, leading to potentiation of apoptosis induced by cytokine and chemotherapeutic agent, J. Biol. Chem., 281, 17023, 2006. 

Chowdhury SA et al (2005) Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids. Anticancer Res 25(3B) 2055-2063... 

FIG. 3. Apoptosis regulation at the MBT. The figure denotes the relative resistance of the embryo after the MBT to apoptosis induced by ionizing radiation (IR, X-rays) and the multiple mechanisms implicated in this resistance. 

Li WX, Cui CB, Cai B, Yao XS. Labdane-type diterpenes as new cell cycle inhibitors and apoptosis inducers from Vitex trifolia L. J Asian Nat Prod Res 2005 7 95-105. 

Inayat-Hussain SH, Annuar BO, Din LB, Ali AM, Ross D. Loss of mitochondrial transmembrane potential and caspase-9 activation during apoptosis induced by the novel styryl-lactone goniothalamin in HL-60 leukemia cells. Toxicol In Vitro 2003 17 433-439. 

Chucair, AJ, Rotstein, NP, Sangiovanni, JP, During, A, Chew, EY, and Politi, LE, 2007. Lutein and zeaxanthin protect photoreceptors from apoptosis induced by oxidative stress Relation with docosahexaenoic acid. Invest Ophthalmol Vis Sci 48, 5168-5177. 

Several studies show that carotenoids are able to act as apoptosis inducers by modulating different molecular pathways involved in the apoptotic process, as recently reviewed (Palozza et al., 2004a). 

The involvement of mitochondria in the pro-apoptotic effects of carotenoids has been clearly demonstrated by the fact that P-carotene induces the release of cytochrome c from mitochondria and alters the mitochondrial membrane potential (Aym) in different tumor cells (Palozza et al., 2003a). Moreover, the highly polar xanthophyll neoxanthin has been reported to induce apoptosis in colon cancer cells by a mechanism that involves its accumulation into the mitochondria and a consequent loss of mitochondrial transmembrane potential and releas of cytochrome c and apoptosis-inducing factor (Terasaki et al., 2007). 

Pervaiz S, Hirpara JL, Clement M-V (1998) Caspase proteases mediate apoptosis induced by anticancer preactivated MC540 in human tumor lines. Cancer Lett 128 11-22... 

Sun X et al. RIP3, a novel apoptosis-inducing kinase. J Biol Chem 1999 274 16871-16875. 

K. E. Pace, C. Lee, P. L. Stewart, and L. G. Baum, Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1, J. Immunol., 163 (1999) 3801-3811. 

Brito GAC, Alcantara C, Guerrant RL Effect of glutamine an alanyl-glutamine on apoptosis induced by C. difficile toxin A on intestinal epithelial cells. Am J Trap Med Hyg 2001 65(suppl) 293. 

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