Targeting protein kinase C (PKC) and telomerase by phenethyl isothiocyanate (PEITC) sensitizes PC-3 cells towards chemotherapeutic drug-induced apoptosis.
Prostate cancer is the leading cause of cancer-related death in men, incidences of which are increasing gradually in India. Protein kinase C (PKC), an enzyme, gets overexpressed in prostate cancer and results in a resistance to chemotherapy. Telomerase, a reverse transcriptase, is highly activated in prostate cancer cells. Both of these enzymes can be considered as potential molecular markers for prostate cancer. The present study investigates the effects of natural isothiocyanate phenethyl isothiocyanate (PEITC) in modulating the activities of PKC and telomerase in the androgen-independent human prostate adenocarcinoma (PC-3) cell line. We observed that PEITC downregulated the antiapoptotic isoforms (PKC alpha and epsilon) efficiently and zeta moderately. Basal level of PKC delta, a proapoptotic form, was very poor and its modulation was not significant. PEITC also inhibited the activity of telomerase. Studies were conducted to measure the degree of apoptotic cell death induced either by PEITC alone or in combination with adriamycin or etoposide. Apoptosis was evident from the release of mitochondrial cytochrome c, apoptotic index, and by the induction of caspases 3 and 8. PEITC exhibited remarkable efficacy in sensitizing PC-3 cells to undergo cell death by adriamycin and etoposide, which might prove to be of considerable value in synergistic therapy of cancer.
Mukherjee
Sutapa
S
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Kolkata 700026, India.
Bhattacharya
Rathindra Kumar
RK
Roy
Madhumita
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D017879:Isothiocyanates; D005047:Etoposide; C058305:phenethyl isothiocyanate; D004317:Doxorubicin; D045304:Cytochromes c; D011493:Protein Kinase C; D019098:Telomerase; D020169:Caspases