Destruction of the cellular antioxidant pool contributes to resveratrol‐induced senescence and apoptosis in lung cancer

Abstract

Resveratrol (RES) has various pharmacological bioactivities and its anticancer effects in lung cancer have been proven. However, the underlying mechanisms of action of RES in lung cancer remain unclear. This study focused on Nrf2-mediated antioxidant systems in RES-treated lung cancer cells. A549 and H1299 cells were treated with various concentrations of RES at different times. RES decreased cell viability, inhibited cell proliferation, and increased the number of senescent and apoptotic cells in a concentration-and time-dependent manner. Moreover, RES-induced lung cancer cell arrest at the G1 phase was accompanied by changes in apoptotic proteins (Bax, Bcl-2, and cleaved caspase 3). Furthermore, RES induced a senescent phenotype along with changes in senescence-related markers (senescence-associated β-galactosidase activity, p21, and p-γH2AX). More importantly, with prolonged exposure time and increased exposure concentration, intracellular reactive oxygen species (ROS) continuously accumulated, resulting in a decrease in Nrf2 and its downstream antioxidant response elements, including CAT, HO-1, NQO1, and SOD1. Meanwhile, RES-induced ROS accumulation and cell apoptosis were reversed by N-acetyl-Lcysteine treatment. Taken together, these results suggest that RES disturb lung cancer cellular homeostasis by destroying the intracellular antioxidant pool to increase ROS production. Our findings provide a new perspective on RES intervention in lung cancer.

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“…If we consider the whole population, senescence and apoptosis are not contradictory. For example, Liang et al found that resveratrol promotes lung cancer cell apoptosis and induces cellular oxidative stress with accompanying senescence phenotypes (Liang et al, 2023). In our view, the coexistence of RGC apoptosis and aging is a key factor in causing visual nerve damage.…”

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“…The anticancer potential of resveratrol was also investigated against lung cancer lines A549 and H1299 in a study by Liang et al (2023) [17]. The authors observed a remarkable decrease in cell viability for A549 and H1299 cells at concentrations of 50 µM and 25 µM, respectively, after 24 h. However, in 48 h, cell viability was significantly inhibited by about 50% at 25 µM for H1299 and A549 cells.…”

“…This bioactive compound has an antioxidant action resulting in several health benefits. Furthermore, research shows that resveratrol also has antimicrobial and antifungal activity [ 34 ] and can be used in the treatment of various diseases, including cancer [ 14 , 17 ].…”

“…Moreover, polyphenols have been extensively researched for their preventive effects on various conditions, such as diabetes, obesity, cardiovascular disease, and neurodegenerative disorders [9,10]. Among the polyphenolic compounds with therapeutic potential, quercetin, curcumin, epigallocatechin-3-gallate (EGCG), and resveratrol have gained a greater prominence in recent years, mainly due to their antioxidant properties, along with pro-oxidant, antiproliferative, anti-angiogenic, and anti-metastatic effects [11][12][13][14][15][16][17]. Despite the high curative potential, a low solubility and poor bioavailability hinder the proper gastrointestinal (GI) absorption of these phytonutrients [7].…”

GutEggerthella lentapromotes the efficacy of resveratrol through reductive metabolism

“…Resveratrol (RSV) is a natural polyphenol abundant in various berries and foods 5 . It has diverse biological activities such as antitumor 6 , anti-inflammatory 7 , anti– cardiovascular disease 8 , and antioxidant effects 9 . RSV exhibits a significant effect on gut microbiota.…”