Oxidative Phosphorylation: A Target for Novel Therapeutic Strategies Against Ovarian Cancer

Abstract

Aerobic glycolysis is an important metabolic adaptation of cancer cells. There is growing evidence that oxidative phosphorylation is also an active metabolic pathway in many tumors, including in high grade serous ovarian cancer. Metastasized ovarian tumors use fatty acids for their energy needs. There is also evidence of ovarian cancer stem cells privileging oxidative phosphorylation (OXPHOS) for their metabolic needs. Metformin and thiazolidinediones such as rosiglitazone restrict tumor growth by inhibiting specific steps in the mitochondrial electron transport chain. These observations suggest that strategies to interfere with oxidative phosphorylation should be considered for the treatment of ovarian tumors. Here, we review the literature that supports this hypothesis and describe potential agents and critical control points in the oxidative phosphorylation pathway that can be targeted using small molecule agents. In this review, we also discuss potential barriers that can reduce the efficacy of the inhibitors of oxidative phosphorylation.

StanDep: Capturing transcriptomic variability improves context-specific metabolic models

“…Among these was also 6 subunits of cytochrome C oxidase, an enzyme belonging to oxidative phosphorylation. Recently, oxidative phosphorylation has garnered interest for targeting cancer due to its important role in dissipation of excess electrons [42]. While the reaction itself was present in both sets of models, only StanDepderived models accurately identified them as essential.…”

Sperm-specific COX6B2 enhances oxidative phosphorylation, proliferation, and survival in human lung adenocarcinoma

“…aspartate) that are required for continued cell division ( Sullivan et al, 2015 ). Third, tumor cells exhibit enhanced sensitivity to inhibitors of OXPHOS ( Nayak et al, 2018 ; Scotland et al, 2013 ). Fourth, isoform switching of complex IV subunits is observed in tumors and is associated with aggressive malignant behaviors ( Oliva et al, 2015 ; Zhang et al, 2016 ; Minton et al, 2016 ).…”

Plumbagin-induced oxidative stress leads to inhibition of Na+/K+-ATPase (NKA) in canine cancer cells

“…Plumbagin is a potent anti-cancer agent that causes cell death in prostate, breast, ovarian and colon cancer cells [20,27,[36][37][38][39][40][41][42]. In the current study, we demonstrate for the first time that plumbagin can also induce apoptotic cell death in canine cancer cell lines.…”