Metabolic Response to the Mitochondrial Toxin 1-Methyl-4-phenylpyridinium (MPP+) in LDH-A/B Double-knockout LS174T Colon Cancer Cells.

ABSTRACT:

Background/aim

Rapid glycolytic substrate-level phosphorylation (SLP) and accumulation of lactic acid are characteristics of diverse cancers. Recent advances in drug discovery have included the use of glycolytic inhibitors with mitochondrial targeting drugs to attempt to invoke an energy crisis in aggressive metabolically active chemo-resistant cancers. In this work, we examine the consequences of inhibiting mitochondrial oxidative phosphorylation (OXPHOS) with 1-methyl-4-phenylpyridinium (MPP+) in LS14T colon cancer cells containing a genetic double knock out (DKO) of lactic acid dehydrogenase (LDHA and LDHB).

Materials and methods

Several metabolic parameters were evaluated concomitant to whole transcriptomic (WT) mRNA, microRNA, and long intergenic non-coding RNAs using A

SUBMITTER: Mack N 

PROVIDER: S-EPMC8240042 | biostudies-literature | 2021 May-Jun

REPOSITORIES: biostudies-literature