A novel mono-carbonyl analogue of curcumin induces apoptosis in ovarian carcinoma cells via endoplasmic reticulum stress and reactive oxygen species production

Mol Med Rep. 2012 Mar;5(3):739-44. doi: 10.3892/mmr.2011.700. Epub 2011 Dec 9.

Abstract

The aim of the present study was to investigate the apoptosis of human ovarian cancer cell lines, A2780 and CP70, induced by a novel curcumin analogue, B19. The proliferation of cells was detected with methyl thiazolyl tetrazolium (MTT) assay and apoptosis was examined by flow cytometry. Reactive oxygen species (ROS) were assessed by the fluorescent indicator DCF-DA. The protein expression of the endoplasmic reticulum (ER) stress pathways, GRP78, XBP-1, ATF-4 and CHOP, was examined with Western blotting. A growth inhibitory effect was observed after treatment with B19 in a dose-dependent manner and with more potential than curcumin. At 20 µM, B19 induced significant apoptosis in CP70 cells. Furthermore, B19 induced the ER stress response, while curcumin had no effect on ER stress. These results suggest that B19 has more effective antitumor properties than curcumin, and is associated with the activation of ER stress and ROS in ovarian cancer cells.

Keywords: curcumin analogues; ovarian cancer; reactive oxygen species; endoplasmic reticulum stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4 / metabolism
  • Apoptosis / drug effects*
  • Carcinoma / metabolism
  • Cell Line, Tumor
  • Curcumin / analogs & derivatives
  • Curcumin / pharmacology*
  • DNA-Binding Proteins / metabolism
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / drug effects*
  • Female
  • Heat-Shock Proteins
  • Humans
  • Ketones / chemistry
  • Ovarian Neoplasms / metabolism
  • Reactive Oxygen Species / metabolism*
  • Receptors, G-Protein-Coupled / metabolism
  • Regulatory Factor X Transcription Factors
  • Transcription Factor CHOP / metabolism
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1

Substances

  • (1E,4E)-1,5-bis(2-methoxyphenyl)penta-1,4-dien-3-one
  • ATF4 protein, human
  • DDIT3 protein, human
  • DNA-Binding Proteins
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Ketones
  • Reactive Oxygen Species
  • Receptors, G-Protein-Coupled
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Activating Transcription Factor 4
  • Transcription Factor CHOP
  • Curcumin