Isothiocyanates sensitize the effect of chemotherapeutic drugs via modulation of protein kinase C and telomerase in cervical cancer cells.
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.
Department of Environmental Carcinogenesis and Toxicology, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, 700 026, India.
Sutapa
S
Mukherjee
Shubhabrata
S
Dey
R K
RK
Bhattacharya
Madhumita
M
Roy
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D019098:Telomerase / Q000187:drug effects* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms
D017879:Isothiocyanates; D005047:Etoposide; C058305:phenethyl isothiocyanate; D004317:Doxorubicin; D011493:Protein Kinase C; D019098:Telomerase; C473643:sulphoraphene