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Journal of Environmental Pathology, Toxicology and Oncology
Facteur d'impact: 1.625 Facteur d'impact sur 5 ans: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Imprimer: 0731-8898
ISSN En ligne: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v28.i4.30
pages 269-282

Targeting Protein Kinase C (PKC) and Telomerase by Phenethyl Isothiocyanate (PEITC) Sensitizes PC-3 Cells Towards Chemotherapeutic Drug-Induced Apoptosis

Sutapa Mukherjee
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Kolkata 700 026
Rathindra Kumar Bhattacharya
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700026
Madhumita Roy
Department of Environmental Carcinogenesis & Toxicology, Chittaranjan National Cancer Institute, Calcutta, India

RÉSUMÉ

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.


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