NADPH homeostasis in cancer: functions, mechanisms and therapeutic implications

Abstract

Nicotinamide adenine dinucleotide phosphate (NADPH) is an essential electron donor in all organisms, and provides the reducing power for anabolic reactions and redox balance. NADPH homeostasis is regulated by varied signaling pathways and several metabolic enzymes that undergo adaptive alteration in cancer cells. The metabolic reprogramming of NADPH renders cancer cells both highly dependent on this metabolic network for antioxidant capacity and more susceptible to oxidative stress. Modulating the unique NADPH homeostasis of cancer cells might be an effective strategy to eliminate these cells. In this review, we summarize the current existing literatures on NADPH homeostasis, including its biological functions, regulatory mechanisms and the corresponding therapeutic interventions in human cancers, providing insights into therapeutic implications of targeting NADPH metabolism and the associated mechanism for cancer therapy.

The double-edged roles of ROS in cancer prevention and therapy

“…NADPH, as the primary hydrogen donor and component of the reducing equivalent pool, maintains moderate disulfide reduction of most proteins through NADPH-dependent TRXR and GR redox systems 80 . Maintaining the dynamic equilibrium of the compartmentalized NADP+/NADPH pools is essential for cellular redox homeostasis and modulation of thiol-disulfide transformation signaling 81 .…”

Lipid Metabolism and Resistance to Anticancer Treatment

“…It was reported that a crucial function of FAO is generating the reducing equivalent NADPH to maintain antioxidant balance. Under stress conditions, cancer cells sustain NADPH levels by increasing FAO and the concomitant downregulation of fatty acid de novo biosynthesis [ 78 ]. Pharmacological inhibition of FAO with the CPT-1 inhibitor, etomoxir, diminishes NADPH levels and glutathione content leading to an elevation of intracellular ROS [ 79 ].…”

Mild Effects of Sunscreen Agents on a Marine Flatfish: Oxidative Stress, Energetic Profiles, Neurotoxicity and Behaviour in Response to Titanium Dioxide Nanoparticles and Oxybenzone

“…After 7 days, GR activity in the intestine decreased in TiO 2 NPs (vs. all the treatments), suggesting impairment of NADPH homeostasis, since GR is an NADPH-dependent oxireductase, and the vulnerability of fish exposed to this NPs towards oxidative stress processes. NADPH is a reducing agent that is critical for an effective antioxidant response [ 57 ]. Data from the literature indicate that the fish intestine is prone to generate reactive oxygen species (ROS) due to its high content in polyunsaturated fatty acids [ 58 ].…”