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KMID : 0617220020130010147
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Duksung Bulletin Phamaceutical Sciences
2002 Volume.13 No. 1 p.147 ~ p.155
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Asiatic acid a triterpene, induces apoptosis through intracellular Ca^2+ release and enhanced expression of p53 in HepG2 human hepatoma cells
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Lee, Yong Soo
Jin, Da-Qing/Kwon, Eun Jin/Park, Seung Hee/Lee, Eung-Seok/Jeong, Tae Cheon/Nam, Doo Hyun
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Abstract
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Asiatic acid (AA), a triterpene, decreased viability and induced apoptosis of HepG2 human hepatoma cells in a dose-dependent manner. AA also markedly increased intracellular Ca^2+ level, which was blocked by TMB-8 and dantrolene, intracellular Ca^2+ release blockers, but not by EGTA, an extracellular Ca^2+ chelator. Moreover, AA-induced apoptosis was significantly suppressed by treatment with TMB-8 and dantrolene suggesting that intracellular Ca^2+ release many play an essential role in the AA-induced apoptosis. In addition, AA profoundly increased protein level of p53, which was also inhibited by BAPTA/AM, an intracellular Ca^2+ chelator, TMB-8 and dantrolene. Treatment with A23187, a Ca^2+ inoophore, or thapsigargin, a Ca^2+ -ATPase inhibitor, alone enhanced p53 nuclear accumulation, indicating that p53 accumulation is dependent on intracellular Ca^2+ increase. Furthermore, the viability of Hep3B, p53-null cells, was much higher than that of HepG2, p53-wild type cells, when treated with AA. Taken together, these results suggest that AA induced apoptosis through increased intracellular Ca^2+, which, in turn, enhanced p53 expression in HepG2 cells. These results further suggest that AA may be a valuable agent for the therapeutic intervention of human hepatomas. ⓒ 2002 Elsevier Science Ireland Ltd. All rights reserved.
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