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

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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.

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Acknowledgements

This work was partially supported by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Science and Culture of Japan (20K07085).

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  1. Risako Onodera and Aiko Sakai have contributed equally to this work.

Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1, Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan

    Risako Onodera, Aiko Sakai, Azumi Tokuda, Taishi Higashi & Keiichi Motoyama

  2. Priority Organization for Innovation and Excellence, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan

    Taishi Higashi

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  1. Risako Onodera
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Correspondence to Keiichi Motoyama.

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Onodera, R., Sakai, A., Tokuda, A. et al. The effect of folate-appended methyl-β-cyclodextrin increases on survival rates in a peritoneal dissemination mouse models of human ovarian cancer. J Incl Phenom Macrocycl Chem 102, 143–149 (2022). https://doi.org/10.1007/s10847-021-01109-y

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