Molecular mechanisms of echinocystic acid-induced apoptosis in HepG2 cells

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• 作者：Tong ; Xuhui ; Lin ; Shigang ; Fujii ; Makoto ; Hou ; De-Xing
• 关键词：Echinocystic acid ; Apoptosis ; Mitochondria ; MAP kinases ; HepG2
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：August 27, 2004
• 年：2004
• 卷：321
• 期：3
• 页码：539-546
• 全文大小：591 K

文摘

Echinocystic acid (EA), a natural triterpone enriched in various herbs, has been showed to have cytotoxic activity in some cancer cells, and is used for medicinal purpose in many Asian countries. In the present study, we found that EA could induce apoptosis in human HepG2 cells, as characterized by DNA fragmentation, activation of caspase-3, -8, and -9, and PARP cleavage. The efficacious induction of apoptosis was observed at 45??M for 24h. Molecular data showed that EA induced the truncation of Bid protein and reduction of Bcl-2 protein. EA also caused the loss of mitochondrial membrane potential (????_m) and cytochrome c release from mitochondria to cytosol. Moreover, EA could activate c-Jun NH₂-terminal kinase (JNK) and p38 kinase, and JNK-specific inhibitor SP600125 and p38 kinase-specific inhibitor SB200235 could block serial molecular events of EA-induced apoptosis such as Bid truncation, Bcl-2 reduction, cytochrome c release, caspase activation, and DNA fragmentation in HepG2 cells. These findings indicate that JNK- and p38 kinase-mediated mitochondrial pathways might be involved in EA-induced apoptosis and enhance our understanding of the anticancer function of EA in herbal medicine.