4.7 Article

Role of fatty acid chain length on the induction of apoptosis by newly synthesized catechin derivatives

期刊

CHEMICO-BIOLOGICAL INTERACTIONS
卷 185, 期 3, 页码 182-188

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2010.02.045

关键词

Catechin; Reactive oxygen species; Mitochondrial membrane potential; Cytochrome c; Caspase; Apoptosis

资金

  1. Toyama higher education foundation
  2. University of Toyama, Japan

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The catechins, a family of polyphenols found in tea, can evoke various responses, including apoptosis. In this study we investigated whether the chemical modification of (-)-epigallocatechin gallate (EGCG) could enhance its apoptosis activity. We found that one of the catechin conjugated with capric acid [(2R,3S)-3',4',5,7-tetrahydroxyflavan-3-yl decanoate; catechin-Cl 0] was most potent to induce apoptosis in U937 cells. C10 treatment resulted in a significant increase in reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) loss, cytochrome c release caspase-9 and caspase-3 activation. In addition to this Cl 0 also activated extrinsic pathway significantly as evident by time-dependent increase in Fas expression and caspase-8 activity. C10 mediated cleavage of Bid may be an important event for cross talk between intrinsic and extrinsic signaling. Moreover, pre-treatment of cells with anti-oxidant N-acetyl-L-cysteine (NAC) significantly prevented C10-induced apoptosis but did not protect MMP loss. Treatment of cells with pan-caspase inhibitor significantly inhibited apoptosis indicating that caspases are playing key role. In addition to this C10 was found to induce apoptosis in human colon cancer (HCT116) cells while it showed resistance to human keratinocytes (HaCat). In short our results showed that the optimal fatty acid side chain length is required for the apoptosis inducing activity of catechin derivatives in U937 cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

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