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Antitumor Effects of Camptothecin Combined with Conventional Anticancer Drugs on the Cervical and Uterine Squamous Cell Carcinoma Cell Line SiHa.
MedLine Citation:
PMID:  19885006     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Sang Won Ha; Yun Jeong Kim; Wonyong Kim; Chung Soo Lee
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Publication Detail:
Type:  Journal Article     Date:  2009-04-30
Journal Detail:
Title:  The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology     Volume:  13     ISSN:  1226-4512     ISO Abbreviation:  Korean J. Physiol. Pharmacol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-11-03     Completed Date:  2011-07-14     Revised Date:  2013-05-23    
Medline Journal Info:
Nlm Unique ID:  9709505     Medline TA:  Korean J Physiol Pharmacol     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  115-21     Citation Subset:  -    
Affiliation:
Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea.
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