Isothiocyanates Sensitize the Effect of Chemotherapeutic Drugs Via Modulation of Protein Kinase C and Telomerase in Cervical Cancer

Isothiocyanates sensitize the effect of chemotherapeutic drugs via modulation of protein kinase C and telomerase in cervical cancer cells

Mol Cell Biochem. 2009 Oct;330(1-2):9-22. Epub 2009 Apr 12.

Mukherjee S, Dey S, Bhattacharya RK, Roy M.

Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, 700 026, India.

Abstract

Isothiocyanates have potential chemopreventive and antitumor effects. In the present study, we examined the actions of PEITC and sulphoraphane in modulating the activity of protein kinase C (PKC) and telomerase in cervical cancer cell line HeLa. These tumor markers are highly activated in human cancers. These compound efficiently downregulated the antiapoptotic isoforms (PKC-alpha, -betaII, -epsilon, and -zeta) as well as telomerase, whereas the proapoptotic form (PKC-delta) was upregulated. Studies were performed to measure the degree of apoptotic cell death induced by either isothiocyanates alone, or in combination with adriamycin or etoposide. Apoptosis was evident from mitochondrial cytochrome c release, apoptotic index and caspases 3 and 8 activation. Results showed that pretreatment exhibited better efficacy in sensitizing HeLa cells toward apoptosis by modulating PKCs, telomerase. This effect of isothiocyanates might prove to be of considerable value in synergistic therapy of cancer such that the drug dose level could be minimized.