Resveratrol

 

• Inhibits proliferation, migration and invasion via Akt and ERK1/2 signaling pathways in renal cell carcinoma cells

• Promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism.

• Resveratrol inhibited proliferation and induced apoptosis in JAK2(V617F) mutant tumor cells and its selectivity was 1.5-6.9 times greater than that observed in other tumor cells without the JAK2(V617F) mutation.

• Improves health and survival of mice on a high-calorie diet, 2016. All cause mortality HR=0.69 (p=0.02). 

• Extended the lifespan of diverse species including Saccharomyces cerevisiae, C elegans and Drosophila melanogaster. 

• ITP testing found 4% median life extension in biologically diverse mice (link).

 

Health Benefits of Resveratrol in Kidney Disease: Evidence from In Vitro and In Vivo Studies

Treatment of ACHN and A498 renal carcinoma cells with RSV resulted in significantly impaired cell growth, cell-to-cell contact, and migration. RSV treatment promoted cell apoptosis and pro-apoptotic protein expression. Limited studies indicate protective effects of RSV against renal cancer.

All available in vitro and in vivo animal and human studies examining the effects of RSV in kidney disease indicate that it can reduce fibrosis, mesangial expansion, oxidative stress, and inflammatory cytokine levels, while improving kidney structure and function. 

 

Resveratrol promotes regression of renal carcinoma cells via a renin-angiotensin system suppression-dependent mechanism, 2017

 

The aim of the present study was to investigate the effect of resveratrol on renal carcinoma cells and explore possible renin-angiotensin system-associated mechanisms. Subsequent to resveratrol treatment, the cell viability, apoptosis rate, cytotoxicity levels, caspase 3/7 activity and the levels of angiotensin II (AngII), AngII type 1 receptor (AT1R), vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) were evaluated in renal carcinoma cells. The effects of AngII, AT1R, VEGF and COX-2 on resveratrol-induced cell growth inhibition and apoptosis were also examined. The results indicated that resveratrol treatment may suppress growth, induce apoptosis, and decrease AngII, AT1R, VEGF and COX-2 levels in renal carcinoma ACHN and A498 cells. In addition, resveratrol-induced cell growth suppression and apoptosis were reversed when co-culturing with AT1R or VEGF. Thus, resveratrol may suppress renal carcinoma cell proliferation and induce apoptosis via an AT1R/VEGF pathway.

 

Resveratrol inhibits proliferation, migration and invasion via Akt and ERK1/2 signaling pathways in renal cell carcinoma cells, 2018

 

Recent studies have shown that resveratrol (RES) inhibits cancer cell growth, migration and invasion. Here, we evaluated RES in two human renal cell carcinoma (RCC) cell lines, ACHN and A498. We investigated the effects of RES on proliferation, cell morphology, colony formation, migration, and invasion. We used a proliferation assay to demonstrate that RES inhibited cell growth with IC50 values 132.9±1.064μM in ACHN, and 112.8±1.191μM in A498, respectively. Using inverted contrast microscopy, we showed that RES reduced cell-to-cell contact and inhibited formation of filopodia. A wound healing assay showed that RES inhibited migration of RCC cells. A Transwell assay showed that RES inhibited RCC migration and invasion. Western blot analysis showed that RES suppresses expression of N-cadherin, Vimentin, Snail, MMP-2, MMP-9, p-Akt and p-ERK1/2, but increased expression of E-cadherin and TIMP-1. In the presence of PD98059, the inhibitor of ERK1/2 pathway, we repeated all of the above experiments, showed that RES acted via the ERK1/2 pathway. Taken together, our results suggested that RES suppressed RCC cell proliferation, migration, and invasion in a concentration- and time-dependent manner. These effects likely resulted from inactivation of the Akt and ERK1/2 signaling pathways.

 

Resveratrol-mediated apoptosis in renal cell carcinoma via the p53/AMPK activated protein kinase/mammalian target of rapamycin autophagy signaling pathway, 2018

Resveratrol, known as phytoalexin, is a natural compound. Clinical studies have revealed that resveratrol has a variety of effects including anti-inflammatory, antivirus and tumor suppressor activities. It has been reported that it may serve an important role in renal cell carcinoma (RCC) however, the molecular mechanism underlying resveratrol-induced apoptosis in RCC is still unclear. The aim of the present study was to determine whether resveratrol could suppress RCC progression. Analysis of apoptosis demonstrated that resveratrol may act as a RCC suppressor in a dose- and time-dependent manner. In addition, the results of the MTT and cell migration experiments revealed that resveratrol significantly decreased cell viability and migration. In addition, the expression of the anti-apoptosis gene B-cell lymphoma 2 (Bcl-2) was downregulated by resveratrol, and the expression of pro-apoptosis gene Bcl-2-associated X was upregulated at the mRNA and protein levels. Resveratrol also promoted the expression of p53 and activated phospho-AMP-activated protein kinase (AMPK). The phosphorylation of mammalian target of rapamycin (mTOR) was inhibited and the autophagy-associated genes, light chain 3, autophagy related (ATG)5 and ATG7, were upregulated at the mRNA and protein levels. In conclusion, resveratrol suppressed RCC viability and migration, and promoted RCC apoptosis via the p53/AMPK/mTOR-induced autophagy signaling pathway.

Lifespan and healthspan extension by resveratrol, 2015

Multiple animal studies suggest that resveratrol may increase lifespan in yeast, worms, flies, bees, fish, and rodents.

Resveratrol is similar to hydroxyurea, which is a chemo drug that causes replicative stress. 

https://www.youtube.com/watch?v=vpxQoGk_ryg

Resveratrol improves health and survival of mice on a high-calorie diet, 2016

Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor- γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

Cox proportional hazards regression shows that resveratrol reduced the risk of death from the HC diet by 31% (hazard ratio = 0.69, P = 0.020)

Resveratrol selectively induces apoptosis in malignant cells with the JAK2V617F mutation by inhibiting the JAK2 pathway, 2015

Scope: Resveratrol is a natural occurring polyphenol with several health promoting activities, including anticancer potential. Here, we analyzed the cytotoxic effects of resveratrol against malignant cells characterized by aberrant activation of the Janus kinase 2 (JAK2).

Methods and results: Cell-cycle analysis, proliferation, apoptosis, and Western blotting assays were performed to study the effect of resveratrol on malignant cells exhibiting an excessive activation of the JAK2 pathway secondary to the JAK2(V617F) mutation. Resveratrol inhibited proliferation and induced apoptosis in JAK2(V617F) mutant tumor cells and its selectivity was 1.5-6.9 times greater than that observed in other tumor cells without the JAK2(V617F) mutation. In addition, resveratrol inhibited the phosphorylation of JAK1, JAK2, and Tyk2 and their downstream mediators, including STAT3 and STAT5. In primary cultures, resveratrol treatment inhibited erythroid progenitor colony formation in blood samples obtained from JAK2(V617F) polycythemia vera patients. Moreover, resveratrol synergized with the selective JAK2 inhibitor ruxolitinib, eliminating tumor cells with the JAK2 mutation.

Conclusion: Resveratrol may have therapeutic potential against myeloproliferative neoplasms associated with the aberrant activation of the JAK2 pathway.