Folate acid-Cyclodextrin/Docetaxel induces apoptosis in KB cellsviathe intrinsic mitochondrial pathway and displays antitumor activityin vivo

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Abstract

Docetaxel (DTX) is an antitumor therapeutic drug limited by solubility and selective delivery tissues. We previously prepared DTX/folate acid-Cyclodextrin (FA-CD) inclusion complexes that target folate receptors of tumor cells and showed that these complexes inhibited cancer cell proliferation by inducing apoptosis. Here we further determined the antitumor effect and apoptotic mechanism of DTX/FA-CD. DTX/FA-CD induced reactive oxygen species-mediated mitochondrial apoptosis in KB cells. DTX/FA-CD led to apoptosis accompanied with the repression of mitochondrial membrane potential and glutathione and overexpression of reactive oxygen species and catalase. DTX/FA-CD also specifically accumulated into tumor regions in KB tumor-bearing mice by active targeting. DTX/FA-CD significantly suppressed tumor growth and showed low toxicity in KB tumor xenografts. We concluded that the DTX/FA-DTX inclusion complex induced the intrinsic mitochondrial-mediated apoptosis to cause cell death. Our results showed favorable antitumor effects of DTX/FA-DTX and indicate DTX/FA-DTX could serve as a safe and effective delivery system for antitumor therapy.

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