Resveratrol inhibits plasma membrane Ca 2+ -ATPase inducing an increase in cytoplasmic calcium

Peterson, Joshua Allen; Oblad, Richard; Mecham, Jeffrey Chad; Kenealey, Jason

doi:10.1016/j.bbrep.2016.06.019

Cited by 11 publications

(18 citation statements)

References 42 publications

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“…[Ca 2+ ] i increases can result from Ca 2+ being retained in the cytosol due to impaired cytosolic Ca 2+ exit, more Ca 2+ entering the cytosol from internal or external Ca 2+ stores, or a combination of these mechanisms. Previous studies have shown that RES activates a rise in [Ca 2+ ] i by inhibition of the plasma membrane Ca 2+ -ATPase (PMCA) and/or by activation of G-proteins, presumably through RES binding to a member of the G-protein coupled receptor (GPCR) family [ 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

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The Effects of 4′-Esterified Resveratrol Derivatives on Calcium Dynamics in Breast Cancer Cells

et al. 2017

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Triple-negative breast cancer is a highly aggressive subtype of breast cancer. Frequently, breast cancer cells modulate their calcium signaling pathways to optimize growth. Unique calcium pathways in breast cancer cells could serve as a way to target tumorigenic cells without affecting normal tissue. Resveratrol has previously been shown to activate calcium signaling pathways. We use cell viability, single-cell calcium microscopy, and RT-PCR assays to determine the activity and mechanism of three different 4′-esterified resveratrol derivatives. We demonstrate that two of the derivatives reduce cell viability more effectively than resveratrol in MDA-MB-231 human breast cancer cells. The derivatives also activate similar pro-apoptotic calcium signaling pathways. In particular, the pivalated and butyrated resveratrol derivatives are intriguing putative chemotherapeutics because they are more effective at decreasing cell viability in vitro and inhibiting the plasma membrane Ca2+-ATPase, a protein that is often modulated in breast cancer.

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Section: Resultsmentioning

confidence: 99%

“…Fura-2 loading and experimental protocols performed were similar to those performed by Peterson et al [ 23 ]. Cells were prepared for imaging by plating to achieve a final cell density of 80,000 cells per well.…”

Section: Methodsmentioning

confidence: 99%

The Effects of 4′-Esterified Resveratrol Derivatives on Calcium Dynamics in Breast Cancer Cells

et al. 2017

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“…More specifically, the resulting elevation of cAMP activates Epac1 [33], which can subsequently activate CaMKII [53]. In addition, RSV has pleiotropic effects on calcium signaling [54] and an increase in intracellular calcium [55] would activate CAMKII. CaMKII is a known eNOS kinase [56], and it can also activate AMPK via CaMKKβ [33].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK

et al. 2020

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We have shown that both insulin and resveratrol (RSV) decrease neointimal hyperplasia in chow-fed rodents via mechanisms that are in part overlapping and involve the activation of endothelial nitric oxide synthase (eNOS). However, this vasculoprotective effect of insulin is abolished in highfat-fed insulin-resistant rats. Since RSV, in addition to increasing insulin sensitivity, can activate eNOS via pathways that are independent of insulin signaling, such as the activation of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), we speculated that unlike insulin, the vasculoprotective effect of RSV would be retained in high-fat-fed rats. We found that high-fat feeding decreased insulin sensitivity and increased neointimal area and that RSV improved insulin sensitivity (p < 0.05) and decreased neointimal area in high-fat-fed rats (p < 0.05). We investigated the role of SIRT1 in the effect of RSV using two genetic mouse models. We found that RSV decreased neointimal area in high-fat-fed wild-type mice (p < 0.05), an effect that was retained in mice with catalytically inactive SIRT1 (p < 0.05) and in heterozygous SIRT1-null mice. In contrast, the effect of RSV was abolished in AMKPα2null mice. Thus, RSV decreased neointimal hyperplasia after arterial injury in both high-fat-fed rats and mice, an effect likely not mediated by SIRT1 but by AMPKα2.

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“…Many naturally occurring compounds such as resveratrol (RES), flavopiridol (FLAV), and piperlongumine (PIP) are multimechanistic compounds that have been identified as putative chemotherapeutics (Pan et al, 2012). Treatment with RES has been shown to cause increases in cytosolic calcium (Ma et al, 2007;Peterson et al, 2016), bind to various proteins to induce intrinsic apoptosis (Locatelli et al, 2005;Calamini et al, 2010;Hsieh et al, 2014), and cause production of ROS (Miki et al, 2012). FLAV inhibits cyclin dependent kinases to disrupt the cell cycle and causes production of ROS (Gupta et al, 2010;Shao et al, 2016), whereas PIP has been shown to cause ROS production and inhibit signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells (Kong et al, 2008;Adams et al, 2012;Ginzburg et al, 2014;Gong et al, 2014;Bharadwaj et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Application of Mixture Design Response Surface Methodology for Combination Chemotherapy in PC-3 Human Prostate Cancer Cells

et al. 2018

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Combining chemotherapeutics to treat malignant tumors has been shown to be effective in preventing drug resistance, tumor recurrence, and reducing tumor size. We modeled combination drug therapy in PC-3 human prostate cancer cells using mixture design response surface methodology (MDRSM), a statistical technique designed to optimize compositions that we applied in a novel manner to design combinations of chemotherapeutics. Conventional chemotherapeutics (mitoxantrone, cabazitaxel, and docetaxel) and natural bioactive compounds (resveratrol, piperlongumine, and flavopiridol) were used in 12 different combinations containing three drugs at varying concentrations. Cell viability and cell cycle data were collected and used to plot response surfaces in MDRSM that identified the most effective concentrations of each drug in combination. MDRSM allows for extrapolation of data from three or more compounds in variable ratio combinations, unlike the Chou-Talalay method. MDRSM combinations were compared with combination index data from the Chou-Talalay method and were found to coincide. We propose MDRSM as an effective tool in devising combination treatments that can improve treatment effectiveness and increase treatment personalization, because MDRSM measures effectiveness rather than synergism, potentiation, or antagonism.

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Resveratrol inhibits plasma membrane Ca 2+ -ATPase inducing an increase in cytoplasmic calcium

Cited by 11 publications

References 42 publications

The Effects of 4′-Esterified Resveratrol Derivatives on Calcium Dynamics in Breast Cancer Cells

The Effects of 4′-Esterified Resveratrol Derivatives on Calcium Dynamics in Breast Cancer Cells

Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK

Application of Mixture Design Response Surface Methodology for Combination Chemotherapy in PC-3 Human Prostate Cancer Cells

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