Effects of isocamptothecin, a novel camptothecin analogue, on proliferation, apoptosis and telomerase activity in HaCaT cells

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Abstract

Camptothecin is a topoisomerase I inhibitor with definite anti-psoriatic effect. As it is limited in clinical application because of serious side effects and toxicity, many researchers are striving hard to develop derivatives or analogues of camptothecin with higher effects and less toxicity. To explore the anti-psoriatic potential of isocamptothecin, a novel camptothecin analogue, its effects on proliferation, apoptosis and telomerase activity were investigated in the human keratinocyte cell line HaCaT. Incubation with isocamptothecin resulted in a time- and concentration-dependent inhibition of HaCaT cell proliferation. However, isocamptothecin showed larger inhibitory concentration at 50% than camptothecin, suggesting far less cytotoxicity. In addition, isocamptothecin induced apoptosis in a concentration-dependent manner and induced typical morphologic features of apoptosis in HaCaT cells. Moreover, isocamptothecin downregulated the telomerase activity of HaCaT cells not only at concentrations of apoptosis induction but also at concentration insufficient to induce apoptosis, providing additional mechanisms that further account for its ability to inhibit keratinocytes proliferation and induce apoptosis. These results indicate that isocamptothecin possesses similar effects on keratinocytes with camptothecin, but shows far less cytotoxicity, it may probably become a promising agent for psoriasis therapy.

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