Asiatic acid, a triterpene, induces apoptosis through intracellular Ca2+ release and enhanced expression of p53 in HepG2 human hepatoma cells

Cancer Lett. 2002 Dec 1;186(1):83-91. doi: 10.1016/s0304-3835(02)00260-4.


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 may 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+) ionophore, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Calcium / metabolism*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Pentacyclic Triterpenes
  • Triterpenes / pharmacology*
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / biosynthesis*


  • Antineoplastic Agents
  • Pentacyclic Triterpenes
  • Triterpenes
  • Tumor Suppressor Protein p53
  • asiatic acid
  • Calcium