Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin

International Journal of Nanomedicine
Kazuhisa KameyamaHidetoshi Arima

Abstract

Mitophagy is the specific autophagic elimination system of mitochondria, which regulates cellular survival via the removal of damaged mitochondria. Recently, we revealed that folate-appended methyl-β-cyclodextrin (FA-M-β-CyD) provides selective antitumor activity in folate receptor-α (FR-α)-expressing cells by the induction of autophagy. In this study, to gain insight into the detailed mechanism of this antitumor activity, we focused on the induction of mitophagy by the treatment of FR-α-expressing tumor cells with FA-M-β-CyD. In contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered KB cells, human epithelial cells from a fatal cervical carcinoma (FR-α (+)) through FR-α-mediated endocytosis. The transmembrane potential of isolated mitochondria after treatment with FA-M-β-CyD was significantly elevated. In addition, FA-M-β-CyD lowered adenosine triphosphate (ATP) production and promoted reactive oxygen species production in KB cells (FR-α (+)). Importantly, FA-M-β-CyD enhanced light chain 3 (LC3) conversion (LC3-I to LC3-II) in KB cells (FR-α (+)) and induced PTEN-induced putative kinase 1 (PINK1) protein expression, which is involved in the induction of mitophagy. Furthermore, FA-M-β-CyD had potent antitumor activity in BALB/c ...Continue Reading

Citations

Apr 2, 2019·Chemical & Pharmaceutical Bulletin·Taishi Higashi
Dec 23, 2017·Chemical & Pharmaceutical Bulletin·Khaled Mohamed ElaminHidetoshi Arima
May 8, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Hidetoshi Arima
Feb 5, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Taishi HigashiHidetoshi Arima
Aug 23, 2019·Annual Review of Nutrition·Xuan YangZhenglong Gu
Oct 2, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ryoma YokoyamaKeiichi Motoyama
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiling FengHongxi Xu

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Methods Mentioned

BETA
Assay
electrophoresis
PCR
xenograft
quartz crystal microbalance

Software Mentioned

Mtphagy

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