Resveratrol cytotoxicity is energy‐dependent

Abstract

Resveratrol is a phytochemical that may promote health. However, it has also been reported to be a toxic compound. The molecular mechanism by which resveratrol acts remains unclear. The inhibition of the oxidative phosphorylation (OXPHOS) pathway appears to be the molecular mechanism of resveratrol. Taking this into account, we propose that the cytotoxic properties of resveratrol depend on the energy (e.g., carbohydrates, lipids, and proteins) availability in the cells. In this regard, in a condition with low energy accessibility, resveratrol could enhance ATP starvation to lethal levels. In contrast, when cells are supplemented with high quantities of energy and resveratrol, the inhibition of OXPHOS might produce a low‐energy environment, mimicking the beneficial effects of caloric restriction. This review suggests that investigating a possible complex relationship between caloric intake and the differential effects of resveratrol on OXPHOS may be justified. Practical applications A low‐calorie diet accompanied by significant levels of resveratrol might modify cellular bioenergetics, which could impact cellular viability and enhance the anti‐cancer properties of resveratrol.

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

“…Although RSV induces premature senescence [27][28][29][30][31][32], RSV is also known to inhibit senescence through an unknown mechanism [79]. RSV is widely believed to enhance mitochondrial function [80], despite being a potent inhibitor of mitochondria [81][82][83][84][85]. RSV inhibits oxidative phosphorylation (OXPHOS) activity at two sites: mitochondrial complex I and complex III of the electron transport chain [82,83].…”

Tigecycline causes loss of cell viability mediated by mitochondrial OXPHOS and RAC1 in hepatocellular carcinoma cells

“…One example of OXPHOS-mediated cytotoxicity is resveratrol. It is well documented that alterations in OXPHOS can modify the cytotoxicity of resveratrol, which is related to energy metabolism [ 32 ]. Resveratrol inhibits OXPHOS and in conditions with low energy accessibility, resveratrol can enhance ATP starvation to lethal levels.…”

Resveratrol shortens the chronological lifespan of Saccharomyces cerevisiae by a pro‐oxidant mechanism

“…The impairing of the ETC by resveratrol has been proposed to induce ROS generation via reverse electron transport (Madrigal‐Perez & Ramos‐Gomez, 2016) or by the semiquinones formation (Plauth et al, 2016). Cells might respond to the oxidative damage caused by resveratrol, expressing their antioxidant systems (Madrigal‐Perez & Ramos‐Gomez, 2016; Olivares‐Marin et al, 2019), which may be the cause of the antioxidant phenotype triggered by resveratrol. Moreover, resveratrol pro‐oxidant properties could accelerate the aging process, according to the free radical theory of aging, which postulates that organism's age due to the accumulation of the harmful effects of ROS in cells (Harman, 1956).…”

“…On the other hand, resveratrol also exerts dose‐dependent phenotypes, fitting well with the hormetic behavior, as reported for cellular viability (Calabrese et al, 2010) and pro‐oxidative properties (Plauth et al, 2016). Importantly, a diet‐dependent effect of phenotypes displayed by resveratrol supplementation has also been documented (Olivares‐Marin et al, 2019). For example, resveratrol exhibits a glucose‐dependent effect in chronological aging (Ramos‐Gomez et al, 2017), cellular viability (Madrigal‐Perez et al, 2016), mitochondrial respiration (Madrigal‐Perez et al, 2016), and hydrogen peroxide release (Ramos‐Gomez et al, 2017) in S. cerevisiae .…”