Evaluation of antitumor effects of folate-conjugated methyl-β-cyclodextrin in melanoma

Biological & Pharmaceutical Bulletin
Keiichi MotoyamaHidetoshi Arima

Abstract

Melanoma is a life-threatening disorder and its incidence is increasing gradually. Despite the numerous treatment approaches, conventional systemic chemotherapy has not reduced the mortality rate among melanoma patients, probably due to the induction of toxicity to normal tissues. Recently, we have developed folate-conjugated methyl-β-cyclodextrin (FA-M-β-CyD) and clarified its potential as a new antitumor agent involved in autophagic cell death. However, it remains uncertain whether FA-M-β-CyD exerts anticancer effects against melanomas. Therefore, in this study, we investigated the effects of FA-M-β-CyD on the folate receptor-α (FR-α)-expressing melanoma cell-selective cytotoxic effect. FA-M-β-CyD showed cytotoxic effects in Ihara cells, a human melanoma cell line expressing FR-α. In sharp contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered Ihara cells [FR-α(+)] through FR-α-mediated endocytosis. Additionally, FA-M-β-CyD elicited the formation of autophagosomes in Ihara cells. Notably, FA-M-β-CyD suppressed melanoma growth in BALB/c nude recombinase-activating gene-2 (Rag-2)/Janus kinase 3 (Jak3) double deficient mice bearing Ihara cells. Therefore, these results suggest that FA-M-β-CyD could be utilized as a potent antican...Continue Reading

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Citations

Nov 3, 2015·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Keiichi Motoyama
Apr 2, 2019·Chemical & Pharmaceutical Bulletin·Taishi Higashi
May 8, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Hidetoshi Arima
Apr 2, 2016·Melanoma Research·Cassandra C SkinnerWilliam E Carson
Feb 5, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Taishi HigashiHidetoshi Arima
Jun 21, 2020·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Yoshitaka MatsumotoHideyuki Sakurai

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