Targeting the metabolic plasticity of multiple myeloma with FDA-approved ritonavir and metformin.

ABSTRACT:

Purpose

We have previously demonstrated that ritonavir targeting of glycolysis is growth inhibitory and cytotoxic in a subset of multiple myeloma cells. In this study, our objective was to investigate the metabolic basis of resistance to ritonavir and to determine the utility of cotreatment with the mitochondrial complex I inhibitor metformin to target compensatory metabolism.

Experimental design

We determined combination indices for ritonavir and metformin, impact on myeloma cell lines, patient samples, and myeloma xenograft growth. Additional evaluation in breast, melanoma, and ovarian cancer cell lines was also performed. Signaling connected to suppression of the prosurvival BCL-2 family member MCL-1 was evaluated in multiple myeloma cell lines and tumor lysates. Reliance

SUBMITTER: Dalva-Aydemir S 

PROVIDER: S-EPMC5571862 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature