Ricolinostat suppresses proliferation, promotes apoptosis, and enhances the antiproliferative activity of topoisomerase inhibitors in cervical cancer cells.

ABSTRACT

Ricolinostat has been found to exhibit anticancer effects alone and in combination with various chemotherapeutic drugs in several cancer types. However, to the best of our knowledge, the efficacy of ricolinostat in cervical cancer is still not investigated. Therefore, in this study, we evaluated the effect of ricolinostat in cervical cancer alone and in combination with topoisomerase inhibitors. The effect of ricolinostat on cervical cancer cells was assessed using MTT, cell-cycle arrest, Annexin V/PI staining assay, reactive oxygen species (ROS) measurement, and western blot analysis. The antiproliferative effect of ricolinostat in combination with topoisomerase inhibitors was assessed using the MTT assay and synergism was computed using "CompuSyn" software. We found that ricolinostat inhibited proliferation, and induced G2/M phase arrest and apoptosis in cervical cancer cells. We further found that ricolinostat treatment resulted in increased ROS production, decreased Bcl-xL expression, and induced p21 expression. We also investigated the effect of ricolinostat in combination with topotecan and etoposide in cervical cancer cells. Ricolinostat was found to significantly enhance the antiproliferative activity of both, topotecan and etoposide, in cervical cancer cells in a concentration-dependent manner. In conclusion, our study showed that ricolinostat suppressed proliferation by inducing G2/M phase arrest and promoted apoptosis in cervical cancer cells, indicating that ricolinostat may be a promising antitumor agent in cervical cancer. Also, ricolinostat and topotecan/etoposide combination are synergistic in cervical cancer cells.