Drastically elevated glycolytic activity is a prominent metabolic feature of
cancer cells. Until recently it was thought that
tumor cells shift their entire energy production from oxidative phosphorylation (OXPHOS) to glycolysis. However, new evidence indicates that many
cancer cells still have functional OXPHOS, despite their increased reliance on glycolysis. Growing pre-clinical and clinical evidence suggests that targeting mitochondrial metabolism has anti-
cancer effects. Here, we analyzed mitochondrial respiration and the amount and activity of OXPHOS complexes in four
melanoma cell lines and normal human dermal fibroblasts (HDFs) by Seahorse real-time cell metabolic analysis, immunoblotting, and spectrophotometry. We also tested three clinically approved
antibiotics, one anti-parasitic
drug (
pyrvinium pamoate), and a novel anti-
cancer agent (
ONC212) for effects on mitochondrial respiration and proliferation of
melanoma cells and HDFs. We found that three of the four
melanoma cell lines have elevated glycolysis as well as OXPHOS, but contain dysfunctional mitochondria. The
antibiotics produced different effects on the
melanoma cells and HDFs. The anti-parasitic
drug strongly inhibited respiration and proliferation of both the
melanoma cells and HDFs.
ONC212 reduced respiration in
melanoma cells and HDFs, and inhibited the proliferation of
melanoma cells. Our findings highlight
ONC212 as a promising
drug for targeting mitochondrial respiration in
cancer.