Lipid Catabolism and ROS in Cancer: A Bidirectional Liaison

Abstract

Although cancer cell metabolism was mainly considered to rely on glycolysis, with the concomitant impairment of mitochondrial metabolism, it has recently been demonstrated that several tumor types are sustained by oxidative phosphorylation (OXPHOS). In this context, endogenous fatty acids (FAs) deriving from lipolysis or lipophagy are oxidised into the mitochondrion, and are used as a source of energy through OXPHOS. Because the electron transport chain is the main source of ROS, cancer cells relying on fatty acid oxidation (FAO) need to be equipped with antioxidant systems that maintain the ROS levels under the death threshold. In those conditions, ROS can act as second messengers, favouring proliferation and survival. Herein, we highlight the different responses that tumor cells adopt when lipid catabolism is augmented, taking into account the different ROS fates. Many papers have demonstrated that the pro- or anti-tumoral roles of endogenous FA usage are hugely dependent on the tumor type, and on the capacity of cancer cells to maintain redox homeostasis. In light of this, clinical studies have taken advantage of the boosting of lipid catabolism to increase the efficacy of tumor therapy, whereas, in other contexts, antioxidant compounds are useful to reduce the pro-survival effects of ROS deriving from FAO.

EPHX2 Inhibits Colon Cancer Progression by Promoting Fatty Acid Degradation

“…The liposome-mediated lipid catabolism affects the production of ROS, because the electron transport chain of mitochondria is the main location of their production. Cancer cells generally have higher levels of ROS to promote proliferation or invasion, but higher than the threshold level of ROS can strongly promote cancer cell apoptosis or iron death, thus inhibiting tumor progression ( 38 – 40 ). This dual effect of ROS on cancer cells must be considered when predicting the mechanism and characteristics of cancer cells’ response to lipid metabolism changes.…”

Structural, antioxidant, and immunomodulatory activities of an acidic exopolysaccharide from Lactiplantibacillus plantarum DMDL 9010

“…Induced by hydrogen peroxide, cells produce large amounts of the oxidant ROS, which converts lipid components of the cell membrane into lipid peroxides. Subsequently, lipid peroxides are degraded to MDA ( 25 ). Simultaneously, with cell membrane destruction, a large amount of lactate dehydrogenase overflows from cells.…”

Metabolic Reprogramming in Cancer Cells: Emerging Molecular Mechanisms and Novel Therapeutic Approaches

“…In a similar manner, lipids play a major role during cancinogenesis by increasing fatty acid uptake through the expression of specialized transporters. Together with augmented de novo lipogenesis, beta oxidation of fatty acids, and altered lipid storage, lipids are related to a more aggressive phenotype, resulting in increased cell migration and evasion of apoptosis [17,18].…”

“…The accumulation of fatty acids by lipogenesis results in their storage in LDs, and cytoplasmic lipases catalyze their output. Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and monoacylglycerol lipase (MAGL) sustain tumor survival [18].…”

“…It produces an increase in the formation of ROS, which have multiple protumorigenic effects by facilitating cell proliferation, tumor growth, and adaptation through their participation in multiple signaling pathways, among which stand out the following: the mitogen-activated protein kinase (MAPK) cascades, phosphoinositide-3-kinase (PI3K)/Akt, and the nuclear factor kappa light chain-enhancer of activated B cell (NF-kB) pathways. Therefore, the correlation between lipid catabolism and ROS production is important in regulating cancer growth and progression [18,35].…”