Molecular Mechanism Behind the Synergistic Activity of Diphenylmethyl Selenocyanate and Cisplatin Against Murine Tumor Model
Somnath Singha Roy,
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.
Rights & PermissionsPrintExport