Mohammad , N. and Singh , S.V. and Malvi , P. and Chaube , B. and Athavale , D. and Vanuopadath , M. and Nair , S.S. and Nair , B. and Bhat , M.K. (2015) Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl- β-cyclodextrin: Involvement of p53 and Fas receptor ligand complex. Scientifc Report . pp. 1-12.

Preview

Text 50.Dr. Bhat (Scientific Report) open access.pdf Download (826Kb) | Preview

Abstract

Doxorubicin (DOX) is one of the preferred drugs for treating breast and liver cancers. However, its clinical application is limited due to severe side effects and the accompanying drug resistance. In this context, we investigated the effect on therapeutic efficacy of DOX by cholesterol depleting agent methyl-β-cyclodextrin (MCD), and explored the involvement of p53. MCD sensitizes MCF-7 and Hepa1-6 cells to DOX, Combination of MCD and marginal dose of DOX reduces the cell viability, and promoted apoptosis through induction of pro-apoptotic protein, Bax, activation of caspase-8 and caspase-7, down regulation of anti-apoptotic protein Bcl-2 and finally promoting PARP cleavage. Mechanistically, sensitization to DOX by MCD was due to the induction of FasR/FasL pathway through p53 activation. Furthermore, inhibition of p53 by pharmacological inhibitor pifithrin-α (PFT-α) or its specific siRNA attenuated p53 function and down-regulated FasR/FasL, thereby preventing cell death. Animal experiments were performed using C57BL/6J mouse isografted with Hepa1-6 cells. Tumor growth was retarded and survival increased in mice administered MCD together with DOX to as compared to either agent alone. Collectively, these results suggest that MCD enhances the sensitivity to DOX for which wild type p53 is an important

Item Type:	Article
Subjects:	Cancer Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	29 Jun 2015 09:22
Last Modified:	25 Feb 2021 11:37
URI:	http://nccs.sciencecentral.in/id/eprint/187

Actions (login required)

View Item