Curcumin induces apoptotic cell death and protective autophagy in human gastric cancer cells

Oncol Rep. 2017 Jun;37(6):3459-3466. doi: 10.3892/or.2017.5637. Epub 2017 May 11.

Abstract

Curcumin possesses an anticancer effect against a wide assortment of tumors with selective cytotoxicity for tumor cells. However, the mechanism involved in the curcumin‑induced anticancer effect remain unclear. In the present study, we investigated the efficacy of curcumin against human gastric cancer cell growth and the molecular mechanism involved. Our results demonstrated that curcumin inhibited the viabilities of gastric cancer cell lines BGC-823, SGC-7901 and MKN-28 in both a time- and dose-dependent manner. In addition, curcumin treatment induced gastric cancer cell apoptosis in a dose‑responsive manner. Western blotting of apoptosis‑related proteins further confirmed the pro-apoptotic potential of curcumin. After exposure to curcumin, a robust induction of autophagy was observed in gastric cancer cells, which was characterized by the formation of acidic vesicular organelles (AVOs), conversion of LC3-I to LC3-II and an increase in the levels of autophagy‑related proteins. Activation of the PI3K/Akt/mTOR signaling pathway was suppressed in gastric cancer cells with curcumin treatment. However, administration of the autophagy inhibitor 3-methyladenine (3-MA) significantly promoted the apoptotic cell death induced by curcumin. Collectively, our findings provide new evidence that curcumin induces apoptotic cell death and protective autophagy in human gastric cancer cells in vitro. Autophagy inhibitor treatment may provide a novel and effective strategy for improving the anticancer effect of curcumin against gastric cancer.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / genetics
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Curcumin / administration & dosage*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • TOR Serine-Threonine Kinases / genetics

Substances

  • Apoptosis Regulatory Proteins
  • 3-methyladenine
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Curcumin
  • Adenine