Molecular mechanism behind the synergistic activity of diphenylmethyl selenocyanate and Cisplatin against murine tumor model.

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.

authors

Chakraborty P,Roy SS,Bhattacharya S

doi

10.2174/1871520615666150113123401

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

501-10

issue

4

eissn

1871-5206

issn

1875-5992

pii

ACAMC-EPUB-64494

journal_volume

15

pub_type

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