Molecular Mechanism Behind the Synergistic Activity of Diphenylmethyl Selenocyanate and Cisplatin Against Murine Tumor Model

Author(s):

Pramita Chakraborty, Somnath Singha Roy and Sudin Bhattacharya   Pages 501 - 510 ( 10 )

Abstract:

Various preclinical, clinical and epidemiological studies have already well established the cancer chemopreventive and chemoprotective potential of selenium compounds. In addition to its protective efficacy, recent studies have also proved the abilities of selenium compounds to induce cell death specifically in malignant cells. Therefore, our intention is to improve the therapeutic efficacy of an alkylating agent, cisplatin, by the adjuvant use of an organoselenium compound, diphenylmethyl selenocyanate (DMSE). It was observed that combined treatment decreased the tumor burden significantly through reactive oxygen species generation and modulation of antioxidant and detoxifying enzyme system in tumor cells. These activities ultimately led to significant DNA damage and apoptosis in tumor cells. Study of the molecular pathway disclosed that the adjuvant treatment caused induction of p53, Bax and suppressed Bcl-2 followed by the activation of caspase cascade. Furthermore, a concomitant decrease in cisplatin-induced nephrotoxicity and hematopoietic toxicity by DMSE might also have enhanced the efficacy of cisplatin and provided survival advantage to the host. Results suggested that the combination treatment with DMSE and cisplatin may offer potential therapeutic benefit, and utilization of cisplatin in cancer chemotherapy exempt of its limitations.

Keywords:

Antioxidant enzymes, apoptosis, cisplatin, DMSE, organoselenium, reactive oxygen species.

Affiliation:

, , Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37- S. P. Mukherjee Road, Kolkata-700026, India.

Graphical Abstract:

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