Crocetin induces cytotoxicity in colon cancer cells via p53-independent mechanisms

Asian Pac J Cancer Prev. 2012;13(8):3757-61. doi: 10.7314/apjcp.2012.13.8.3757.

Abstract

Objective: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro.

Methods: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the TUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclin A and P21 were examined by Western blot analysis.

Results: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) significantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner.

Conclusions: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Carotenoids / pharmacology*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / drug effects*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology*
  • Comet Assay
  • DNA Damage / drug effects*
  • Flow Cytometry
  • Humans
  • Mice
  • Mutation / genetics
  • NIH 3T3 Cells
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Vitamin A / analogs & derivatives
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anticarcinogenic Agents
  • Cell Cycle Proteins
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • trans-sodium crocetinate
  • Vitamin A
  • Carotenoids