Abstract

Melanoma is one of leading cause of tumor death worldwide. Anti-cancer strategy includes combination of different chemo-therapeutic agents as well as radiation; however these treatments have limited efficacy and induce significant toxic effects on healthy cells. One of most promising novel therapeutic approach to cancer therapy is the combination of anti-cancer drugs with calorie restriction. Here we investigated the effect Cisplatin (CDDP), one of the most potent chemotherapeutic agent used to treat tumors, in association with fasting in wild type and mutated BRAF(V600E) melanoma cell lines. Here we show that nutrient deprivation can consistently enhance the sensitivity of tumor cells to cell death induction by CDDP, also of those malignancies particularly resistant to any treatment, such as oncogenic BRAF melanomas. Mechanistic studies revealed that the combined therapy induced cell death is characterized by ROS accumulation and ATF4 in the absence of ER-stress. In addition, we show that autophagy is not involved in the enhanced sensitivity of melanoma cells to combined CDDP/EBSS-induced apoptosis. While, the exposure to 2-DG further enhanced the apoptotic rate observed in SK Mel 28 cells upon treatment with both CDDP and EBSS.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• Antunes F. , Corazzari M. , Pereira G. , Fimia G.M. , Piacentini M. , Smaili S.

Titolo volume/Rivista

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Anno di pubblicazione

2016

ISSN

0006-291X

ISBN

Non Disponibile

Numero di citazioni Wos

3

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

2

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile