Resveratrol inhibits ovarian cancer cell adhesion to peritoneal mesothelium in vitro by modulating the production of α5β1 integrins and hyaluronic acid

Gynecol Oncol. 2014 Sep;134(3):624-30. doi: 10.1016/j.ygyno.2014.06.022. Epub 2014 Jul 1.


Objective: Resveratrol (Res) is known to inhibit adhesion of numerous malignancies though its effect on an adherence of ovarian cancer cells to peritoneal mesothelium remains undefined.

Methods: To address this issue, ovarian cancer cells (A2780, OVCAR-3, SKOV-3) were subjected to Res (10, 50, 100 μM), and then their adhesion to omentum-derived human peritoneal mesothelial cells (HPMCs) was assayed.

Results: The study showed that Res inhibits adhesion of all ovarian cancer cell lines investigated. More importantly, this effect was evident either when cancer cells were directly treated with Res (cell-dependent activity) or when intact cancer cells were pretreated with conditioned medium (CM) generated by their counterparts subjected to Res (medium-dependent activity). Cell-dependent activity of Res has been recognized to be linked with decreased level of cellular α5β1 integrins which decreased functionality corresponds with reduced efficiency of cancer cell adhesion. Medium-related effects have been, in turn, associated with up-regulated secretion of soluble HA to environment (CM). The experiments with exogenous HA revealed the inverse relation between HA concentration in CM and cancer cell adhesion. When the CM from cells subjected with Res (with elevated HA) was supplemented with hyaluronidase, the restoration of cell adhesive capabilities occurred.

Conclusions: Our studies evidenced that Res affects ovarian cancer cell adhesion to HPMCs by decreasing cellular α5β1 integrin level and by increasing the secretion of HA to environment.

Keywords: Adhesion; Hyaluronic acid; Integrins; Ovarian cancer; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Adhesion / drug effects
  • Epithelial Cells
  • Epithelium
  • Female
  • Humans
  • Hyaluronic Acid / biosynthesis*
  • Integrin alpha5beta1 / biosynthesis*
  • Integrin alpha5beta1 / drug effects*
  • Ovarian Neoplasms / pathology*
  • Peritoneum
  • Resveratrol
  • Stilbenes / pharmacology*
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Integrin alpha5beta1
  • Stilbenes
  • Hyaluronic Acid
  • Resveratrol