Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells

Drug Des Devel Ther. 2015 Jun 12:9:3017-30. doi: 10.2147/DDDT.S84448. eCollection 2015.

Abstract

Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma.

Keywords: apoptosis; cell cycle arrest; gallbladder carcinoma; mitochondrial pathway; oleanolic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • G1 Phase / drug effects*
  • Gallbladder Neoplasms / drug therapy*
  • Humans
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Nude
  • Mitochondria / drug effects*
  • Oleanolic Acid / pharmacology*
  • Resting Phase, Cell Cycle / drug effects*
  • Tetrazolium Salts
  • Thiazoles
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Tetrazolium Salts
  • Thiazoles
  • Oleanolic Acid
  • thiazolyl blue