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Original Article

Korean J Physiol Pharmacol 2009; 13(2): 115-122

Published online April 30, 2009 https://doi.org/10.4196/kjpp.2009.13.2.115

Copyright © Korean J Physiol Pharmacol.

Antitumor Effects of Camptothecin Combined with Conventional Anticancer Drugs on the Cervical and Uterine Squamous Cell Carcinoma Cell Line SiHa

Sang Won Ha1, Yun Jeong Kim1, Wonyong Kim2,3, and Chung Soo Lee1

Departments of 1Pharmacology and 2Microbiology, 3Research Institute for Translational System Biomics, College of Medicine, Chung-Ang University, Seoul 156-756, Korea

Abstract

Functional defects in mitochondria are involved in the induction of cell death in cancer cells. We assessed the toxic effect of camptothecin against the human cervical and uterine tumor cell line SiHa with respect to the mitochondria-mediated cell death process, and examined the combined effect of camptothecin and anticancer drugs. Camptothecin caused apoptosis in SiHa cells by inducing mitochondrial membrane permeability changes that lead to the loss of mitochondrial membrane potential, decreased Bcl-2 levels, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH. Combination of camptothecin with other anticancer drugs (carboplatin, paclitaxel, doxorubicin and mitomycin c) or signaling inhibitors (farnesyltransferase inhibitor and ERK inhibitor) did not enhance the camptothecin-induced cell death and caspase-3 activation. These results suggest that camptothecin may cause cell death in SiHa cells by inducing changes in mitochondrial membrane permeability, which leads to cytochrome c release and activation of caspase-3. This effect is also associated with increased formation of reactive oxygen species and depletion of GSH. Combination with other anticancer drugs (or signaling inhibitors) does not appear to increase the anti-tumor effect of camptothecin against SiHa cells, but rather may reduce it. Combination of camptothecin with other anticancer drugs does not seem to provide a benefit in the treatment of cervical and uterine cancer compared with camptothecin monotherapy.

Keywords: Camptothecin, SiHa cells, Mitochondrial membrane permeability change, Cell death, Combined effect of anticancer drugs