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  2. The course of uncarinic acid E-induced apoptosis of HepG2 cells from damage to DNA and p53 activation to mitochondrial release of cytochrome c

The course of uncarinic acid E-induced apoptosis of HepG2 cells from damage to DNA and p53 activation to mitochondrial release of cytochrome c

  • Biol Pharm Bull. 2006 Aug;29(8):1639-44. doi: 10.1248/bpb.29.1639.
Minghong Zhao 1 Tao Guo Minwei Wang Qingchun Zhao Yanxia Liu Xuehui Sun Huailiang Wang Yue Hou
Affiliations

Affiliation

  • 1 The General Hospital of Shenyang Military Region, Shenyang, China.
Abstract

Uncarinic acid E, an active component isolated from Gelsemium elegans BENTH, has been reported to exhibit antitumor effects, but little is known about its molecular mechanisms of action. In this study, the growth-inhibitory activity of uncarinic acid E for HepG2 cells is in time- and dose-dependent manner. HepG2 cells treated with uncarinic acid E exhibited several typical characteristics of Apoptosis through photomicroscopical observation, DNA Agarose gel electrophoresis. The inhibitory effect of uncarinic acid E on HepG2 cells was partially reversed by the inhibitors of pan-caspase, Caspase-3 and caspase-6. The protein expression ratio of Bcl-xL/Bax and Bcl-2/Bax was down-regulated and uncarinic acid E-induced Apoptosis involves the initial phase mediated by the balance among Bcl-xL, Bcl-2 and Bax proteins, resulting in cytochrome c release from the mitochondria. Uncarinic acid E significantly increased the expression of p53 proteins indicates that p53 plays a pivotal role in the initiation phase of uncarinic acid E-induced HepG2 cell Apoptosis. The phoshatidylinositol 3-kinase (PI3-K) family inhibitor wortmanin and the MEK Inhibitor (PD98059) rescued the viability loss induced by uncarinic acid E through the expression of p53. Taken together, uncarinic acid E induces Apoptosis in HepG2 cells via accumulation of p53, alters the Bax/Bcl-2 ratio, and activates caspases, resulting in cytochrome c release from the mitochondria.

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