Anti-proliferative and pro-apoptotic effect of CPT13, a novel camptothecin analog, on human colon cancer HCT8 cell line

Chemico-biological Interactions
Li-Min WangShou-Gang Jiang

Abstract

10-(2-pyrazolyl-ethoxy)-(20S)-camptothecin (CPT13) is a novel semi-synthetic analogue of camptothecin, our previous report had shown that it possessed higher in vitro cytoxicity activity towards human colon cancer HCT8 cell line than topotecan. In this study, the anti-proliferative effect of CPT13 on HCT8 cell line in vitro was analyzed. In order to further explore the underlying mechanism of cell growth inhibition of CPT13 towards HCT8 cell line, the cell cycle distribution, apoptosis proportion, the nuclei morphological changes and caspase-8 and caspase-3 activities were measured. Additionally the changes of mitochondrial morphology and membrane potential (DeltaPsim) were analyzed by atomic force microscopy (AFM) and flow cytometry, respectively. The results showed that CPT13 inhibited HCT8 cell growth by causing cell cycle arrest at G2/M transition and induced apoptosis, as evidenced by the typical apoptotic morphology such as condensation and fragmentation of nuclei and formation of apoptotic bodies. The changes of mitochondrial morphology, dose-dependently decrease in DeltaPsim and the enhancement of caspase-8 and caspase-3 activities were observed in different concentrations of drug treatment group. Our results suggest th...Continue Reading

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