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: Risako Onodera, Keiichi Motoyama, Nao Tanaka, Ayumu Ohyama, Ayaka Okamatsu, Taishi Higashi, Ryusho Kariya, Seiji Okada, Hidetoshi Arima
• Journal: Scientific reports (Sci Rep) Vol. 4 Pg. 4417 (Mar 20 2014) ISSN: 2045-2322 [Electronic] England
• PMID: 24646866 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Folate Receptor 1
• Ligands
• beta-Cyclodextrins
• methyl-beta-cyclodextrin
• Folic Acid

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Autophagy (drug effects)
• Folate Receptor 1 (genetics, metabolism)
• Folic Acid (chemistry)
• Gene Expression
• Humans
• KB Cells
• Ligands
• Protein Binding
• beta-Cyclodextrins (chemical synthesis, pharmacology)