Poster Presentation 25th Lorne Cancer Conference 2013

Monepantel suppress ovarian cancer cell proliferation by arresting cell cycle at G1 and down regulating cycline A and E, Cdk 2 and 4 (#114)

Farnaz Bahrami B. 1 , David L. Morris 1 , Mohammad H. Pourgholami 1
  1. UNSW, Medicine, Kogarah, NSW, Australia

Aims: Ovarian cancer is one of the most widespread and feared diseases in the world - feared largely because it is difficult to cure.  We have discovered that monepantel (MPL) inhibits proliferation of ovarian cancers cell lines.

A novel anthelmintic, MPL has recently been introduced into the market. It belongs to a new class of anthelmintic, the amino-acetonitrile derivative (AADs). It is thought to act via ligand-gated DEG-3/DES-2 channels, unique to nematodes. Thus, it makes MPL, a drug worth to explore for oncology. The aim of our study was therefore examine the potential of MPL as an anticancer agent in ovarian cancer cells in-vitro


Methods: To evaluate the effect of MPL on cell viability and proliferation, ovarian cancer cell lines (OVCAR-3 and A2780) and normal ovarian epithelial cells (HOSE and CHO) were treated with MPL and determined by SRB proliferation assay and trypan blue. FACS was performed to determine the effects of MPL on the cell cycle. Western blot applied and DNA synthesis was quantified with 3H-thymidine incorporation assay.  Light microscopy was used to investigate morphology of the cells during treatment with MPL.

Result: Treatment with MPL suppresses ovarian cancer cell lines' proliferation and colony formation, while it has no significant effect on normal epithelial cells. Monepantel causes G1 cell cycle arrest through down regulation of cycline A, E and Cdk 2 and 4, followed by inhibition of DNA incorporation.


Conclusion: These results demonstrate for the first time the anticancer properties of MPL. Furthermore, our findings show extensive induction of cell death by MPL in these cells thus warranting further investigations.