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Potential use of folate-appended methyl-?-cyclodextrin as an anticancer agent.

ABSTRACT: To obtain a tumor cell-selectivity of methyl-?-cyclodextrin (M-?-CyD), we newly synthesized folate-appended M-?-CyD (FA-M-?-CyD), and evaluated the potential of FA-M-?-CyD as a novel anticancer agent in vitro and in vivo. Potent antitumor activity and cellular association of FA-M-?-CyD were higher than those of M-?-CyD in KB cells, folate receptor (FR)-positive cells. FA-M-?-CyD drastically inhibited the tumor growth after intratumoral or intravenous injection to FR-positive Colon-26 cells-bearing mice. The antitumor activity of FA-M-?-CyD was comparable and superior to that of doxorubicin after both intratumoral and intravenous administrations, respectively, at the same dose, in the tumor-bearing mice. All of the tumor-bearing mice after an intravenous injection of FA-M-?-CyD survived for at least more than 140 days. Importantly, an intravenous administration of FA-M-?-CyD to tumor-bearing mice did not show any significant change in blood chemistry values. These results strongly suggest that FA-M-?-CyD has the potential as a novel anticancer agent.

SUBMITTER: Onodera R

PROVIDER: S-EPMC3551233 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Involvement of autophagy in antitumor activity of folate-appended methyl-β-cyclodextrin.

Project description: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.

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2-Hydroxypropyl-?-Cyclodextrin Acts as a Novel Anticancer Agent.

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Project description: Not available

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