Resveratrol inhibits cell growth in a human cholangiocarcinoma cell line

Liver Int. 2008 Dec;28(10):1426-36. doi: 10.1111/j.1478-3231.2008.01749.x. Epub 2008 Apr 5.

Abstract

Background/aims: Cholangiocarcinoma is a devastating tumour with a poor prognosis. An efficient therapy is unavailable in unoperable patients and new drugs are widely sought for and required. Resveratrol (RES) is a natural molecule with a reported anticancer effect, evaluated on different tumour cell lines. We tested the efficacy of RES on a cholangiocarcinoma cell line for the first time.

Methods: We used the human SK-ChA-1 cell line, cultured in the classical two-dimensional model and in the three-dimensional spheroids. After RES exposure morphology, cell viability (colony-forming assay), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and cancer antigen (CA) 19-9 medium releases, cellular transglutaminase activity, karyotype and cell cycle were evaluated.

Results: Resveratrol inhibited cell growth in both the cell culture systems used (from -15 to -80% vs untreated controls) and induced a 40-fold increase of LDH and ALP activities in the culture medium. Also, transglutaminase (TG) activity increased in the cell lysates, together with a cell cycle perturbation characterised by an accumulation in the G(1)/S phase. Karyotype and CA 19-9 expression were not influenced by the treatment.

Conclusions: The observed cytotoxic effect of RES on the human cholangiocarcinoma SK-ChA-1 cell line cultured two- and three-dimensionally suggests to further analyse its chemotherapic/chemopreventive possibilities for this kind of cancer.

Publication types

  • Comparative Study

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cholangiocarcinoma / drug therapy*
  • Colony-Forming Units Assay
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Karyotyping
  • L-Lactate Dehydrogenase / metabolism
  • Microscopy, Electron, Scanning
  • Resveratrol
  • Stilbenes / pharmacology*
  • Transglutaminases / metabolism

Substances

  • Stilbenes
  • L-Lactate Dehydrogenase
  • Transglutaminases
  • Alkaline Phosphatase
  • Resveratrol