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

DOI Web Site Web Site PubMed 被引用文献8件 参考文献39件
  • Motoyama Keiichi
    Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Onodera Risako
    Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Tanaka Nao
    Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Kameyama Kazuhisa
    Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Higashi Taishi
    Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University
  • Kariya Ryusho
    Division of Hematopoiesis, Center for AIDS Research, Kumamoto University
  • Okada Seiji
    Division of Hematopoiesis, Center for AIDS Research, Kumamoto University
  • Arima Hidetoshi
    Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University Program for Leading Graduate Schools “HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program,” Kumamoto University

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  • Evaluation of Antitumor Effects of Folate-Conjugated Methyl-β-cyclodextrin in Melanoma

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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 anticancer agent for melanoma chemotherapy by regulating autophagy.

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