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

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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-α, -βII, -ε, and -ζ) as well as telomerase, whereas the proapoptotic form (PKC-δ) 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.

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Acknowledgments

The authors gratefully acknowledge Department of Science and Technology (DST), New Delhi, India for their financial assistance in executing this research work and Director, Chittaranjan National Cancer Institute, Kolkata, India for providing infrastructural facilities.

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Authors and Affiliations

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

    Sutapa Mukherjee, R. K. Bhattacharya & Madhumita Roy

  2. Department of Central Research Instrumentation Facility, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, 700 026, India

    Shubhabrata Dey

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  1. Sutapa Mukherjee
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  2. Shubhabrata Dey
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Correspondence to Madhumita Roy.

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Mukherjee, S., Dey, S., Bhattacharya, R.K. et al. Isothiocyanates sensitize the effect of chemotherapeutic drugs via modulation of protein kinase C and telomerase in cervical cancer cells. Mol Cell Biochem 330, 9–22 (2009). https://doi.org/10.1007/s11010-009-0095-4

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