Curcumin-induced autophagy contributes to the decreased survival of oral cancer cells

Arch Oral Biol. 2012 Aug;57(8):1018-25. doi: 10.1016/j.archoralbio.2012.04.005. Epub 2012 May 1.

Abstract

Curcumin, a major active component of turmeric Curcuma longa, has been shown to have inhibitory effects on cancers. In vitro studies suggest that curcumin inhibits cancer cell growth by activating apoptosis, but the mechanism underlying the anticancer effects of curcumin is unclear. Recently, it has been suggested that autophagy may play an important role in cancer therapy. However, little data are available regarding the role of autophagy in oral cancers. In this study, we have shown that curcumin has anticancer activity against oral squamous cell carcinoma (OSCC). Induction of autophagy, marked by autophagic vacuoles formation, was detected by acridine orange staining and monodansylcadaverine (MDC) dye after exposure to curcumin. Conversion of LC3-I to LC3-II, a marker of active autophagosome formation, was also detectable by Western blot following curcumin treatment. We have also observed that curcumin induced reactive oxygen species (ROS) production and autophagic vacuoles formation by curcumin was almost completely blocked in the presence of N-acetylcystein (NAC), an antioxidant. Rescue experiments using an autophagy inhibitor suppressed curcumin-induced cell death in OSCC, confirming that autophagy acts as a pro-death signal. Furthermore, curcumin shows anticancer activity against OSCC via both autophagy and apoptosis. These findings suggest that curcumin may potentially contribute to oral cancer treatment and provide useful information for the development of a new therapeutic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology
  • Acridine Orange
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Blotting, Western
  • Cadaverine / analogs & derivatives
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation / drug effects
  • Curcumin / pharmacology*
  • Flow Cytometry
  • Humans
  • Microtubule-Associated Proteins / metabolism
  • Mouth Neoplasms / drug therapy*
  • Mouth Neoplasms / pathology
  • Reactive Oxygen Species / metabolism
  • Staining and Labeling
  • Tumor Cells, Cultured
  • Vacuoles / drug effects

Substances

  • Antineoplastic Agents
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • Acridine Orange
  • monodansylcadaverine
  • Curcumin
  • Cadaverine
  • Acetylcysteine