title: Involvement of autophagy in antitumor activity of folate-appended methyl-β-cyclodextrin.
abstract: Autophagy, the major lysosomal pathway for recycling intracellular components including organelles, is emerging as a key process regulating tumorigenesis and cancer therapy. Most recently, we newly synthesized folate-appended methyl-β-cyclodextrin (FA-M-β-CyD), and demonstrated the potential of FA-M-β-CyD as a new antitumor drug. In this study, we investigated whether anticancer activity of FA-M-β-CyD in folate receptor-α (FR-α)-positive tumor cells is involved in autophagy. In contrast to methyl-β-cyclodextrin (M-β-CyD), FA-M-β-CyD entered KB cells (FR-α (+)) through CLIC/GEEC endocytosis. No significant depression in the DNA content was observed in KB cells after treatment with FA-M-β-CyD. Additionally, the transmembrane potential of mitochondria after treatment with FA-M-β-CyD was drastically elevated. Meanwhile, FA-M-β-CyD induced the formation of autophagic vacuoles, which were partially colocalized with mitochondria, in KB cells. Taken together, these results suggest that FR-α-expressing cell-selective cytotoxic activity of FA-M-β-CyD could be mediated by the regulation of autophagy, rather than the induction of apoptosis.
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Risako
authors.initials: R
authors.lastname: Onodera
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: 1] Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan [2] Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Ohyama
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Okamatsu
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Ryusho
authors.initials: R
authors.lastname: Kariya
authors.affiliation: Division of Hematopoiesis, Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Okada
authors.affiliation: 1] Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan [2] Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D058975:Folate Receptor 1 / Q000235:genetics* / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry*; D015870:Gene Expression; D006801:Humans; D007624:KB Cells; D008024:Ligands; D011485:Protein Binding; D047392:beta-Cyclodextrins / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D058975:Folate Receptor 1; D008024:Ligands; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D005492:Folic Acid