Involvement of autophagy in antitumor activity of folate-appended methyl-?-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-?-cyclodextrin (FA-M-?-CyD), and demonstrated the potential of FA-M-?-CyD as a new antitumor drug. In this study, we investigated whether anticancer activity of FA-M-?-CyD in folate receptor-? (FR-?)-positive tumor cells is involved in autophagy. In contrast to methyl-?-cyclodextrin (M-?-CyD), FA-M-?-CyD entered KB cells (FR-? (+)) through CLIC/GEEC endocytosis. No significant depression in the DNA content was observed in KB cells after treatment with FA-M-?-CyD. Additionally, the transmembrane potential of mitochondria after treatment with FA-M-?-CyD was drastically elevated. Meanwhile, FA-M-?-CyD induced the formation of autophagic vacuoles, which were partially colocalized with mitochondria, in KB cells. Taken together, these results suggest that FR-?-expressing cell-selective cytotoxic activity of FA-M-?-CyD could be mediated by the regulation of autophagy, rather than the induction of apoptosis.

SUBMITTER: Onodera R 

PROVIDER: S-EPMC3960581 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature