Developing Atovaquone and YM155 as Chemotherapeutic Agents against Ovarian Cancer

Abstract

Atovaquone, an FDA-approved antimalarial drug and YM155, a drug that has cleared Phase II clinical trials for lung cancer and melanoma, reduce the viability of mouse ovarian cancer cells. Both the drugs induce apoptosis in these cells by inducing oxidative stress. Simultaneously, there is also induction of autophagy and increase in the levels of Nrf-2 in the cells, likely reducing the efficacy of the drugs. Usage of inhibitors of either autophagy or Nrf2 could synergistically increase the efficacy of the drugs. Atovaquone, administered orally as Mepron, is found to be effective in decreasing the tumor burden and ascites fluid accumulation in vivo when murine ovarian cancer cells were intraperitoneally implanted in syngeneic C57BL/6 mice. This study, thus, lays out the foundation for further developing the atovaquone and YM155 as chemotherapeutic agents against ovarian cancer.