Protective effect of resveratrol against caspase 3 activation in primary mouse fibroblasts

Abstract

AimTo study the effect of resveratrol on survival and caspase 3 activation in non-transformed cells after serum deprivation.MethodsApoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation and lactate dehydrogenase release were assayed as cell viability measure by using their fluorogenic substrates. The involvement of PI3K, ERK, JNK, p38, and SIRT1 signaling pathways was also examined.ResultsSerum deprivation of primary fibroblasts induced significant activation of caspase 3 within 3 hours and reduced cell viability after 24 hours. Resveratrol dose-dependently prevented caspase activation and improved cell viability with 50% inhibitory concentration (IC50) = 66.3 ± 13.81 µM. It also reduced the already up-regulated caspase 3 activity when it was added to the cell culture medium after 3 hour serum deprivation, suggesting its rescue effect. Among the major signaling pathways, p38 kinase was critical for the protective effect of resveratrol which was abolished completely in the presence of p38 inhibitor.ConclusionResveratrol showed protective effect against cell death in a rather high dose. Involvement of p38 kinase in this effect suggests the role of mild stress in its cytoprotective action. Furthermore due to its rescue effect, resveratrol may be used not only for prevention, but also treatment of age-related degenerative diseases, but in the higher dose than consumed in conventional diet.

Resveratrol induces mitochondria-mediated, caspase-independent apoptosis in murine prostate cancer cells

“…In human lung adenocarcinoma cells, RES stimulates mitochondria-mediated and caspase-dependent cell death [ 88 ]. Conversely, in primary mouse fibroblasts, RES exhibits a cytoprotective effect by acting against caspase-3 [ 89 ]. The present results show that, for TRAMP cells, the caspase-3 inhibitor, z-VAD-fmk, and Nec-1, which blocks necroptosis, had a negligible effect on RES-mediated cell killing.…”

Resveratrol alleviates FFA and CCl4 induced apoptosis in HepG2 cells via restoring endoplasmic reticulum stress

“…However, when the GRP78 gene was down-regulated with siRNA, RSV still played a role in inhibiting apoptosis in the model cells, indicating that the anti-apoptotic effect of RSV was not solely dependent on GRP78 and has an overall inhibitory effect on the ER stress reaction. Actually, studies showed that RSV could protect cells from apoptosis by directly inhibit Caspase-3 [ 46 ], thus the anti-apoptotic effect of RSV might be dependent on both caspase inhibition and ER stress restoration.…”

Resveratrol: A Double-Edged Sword in Health Benefits

“…Besides, in absence of estrogen (E 2 ), resveratrol exerts mixed estrogen agonist/antagonist activities in some mammary cancer cell lines, but in the presence of E 2 , resveratrol acts as an anti-estrogen [ 134 ]. In another report, it was demonstrated that resveratrol abolishes serum deprivation-induced elevated caspase 3 activity, suggesting its rescue effect via p38 MAPK signaling [ 135 ]. Resveratrol also regulates mitochondrial respiratory chain function, with mitochondrial complex I (CI) as a direct target of this molecule.…”