The effect of folate-appended methyl-β-cyclodextrin increases on survival rates in a peritoneal dissemination mouse models of human ovarian cancer

Abstract

Among gynaecological cancers, ovarian cancer is known to be highly sensitive to chemotherapy. However, it is often detected at an advanced stage since it exhibits few early symptoms, and therefore, patients tend to show poor prognosis. Therefore, the development of new anticancer agents for the treatment advanced stage cancers is required. We previously reported that folic acid-modified methyl-β-cyclodextrin (FA-M-β-CyD) is a promising anticancer agent that exhibits selective antitumor activity in cancers cells. However, the antitumor effect of FA-M-β-CyD in ovarian cancer is not known. Therefore, in this study, we investigated the antitumor effect of FA-M-β-CyD in ovarian cancer. FA-M-β-CyD showed excellent cytotoxic activity in the reduced folate carrier (RFC) positive human ovarian cancer ES-2 cells line. We found that the cytotoxic activity of FA-M-β-CyD in ES-2 (RFC+) cells is unlikely to be a result of apoptosis triggered by a decrease in mitochondrial membrane potential. Moreover, FA-M-β-CyD prolonged the survival of BALB/c nude mice bearing ES-2 (RFC+) cells. These results suggest the potential of FA-M-β-CyD as an antitumor agent for treatment of metastatic ovarian cancer.