Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis

Öktem, Gülperi; Uysal, Ayşegül; Oral, Onur; Sezer, Ebru; Olukman, Murat; Erol, Ayşe; Akgür, Serap Annette; Bılır, Ayhan

doi:10.1016/j.etp.2010.11.001

Cited by 69 publications

(30 citation statements)

References 37 publications

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“…Animal studies have indicated that RES enhanced the cytotoxic effects of several chemotherapeutic agents such as 5-fluorouracil, placitaxel, cisplatin and temozolomide, in the same way in vitro studies did [52, 133,144-146], and decreased or delayed carcinogenesis induced by well-known carcinogens such as doxorubicin, diethylnitrosamine, benzo[a]pyrene, 1,2-dimethylhydrazine, 7,12-dimethyl-benz[a]anth-racene, N-nitrosomethylbenzylamine and azoxyme-thane [36,135, 138,143,147-151]. …”

Section: Preclinical Studiesmentioning

confidence: 81%

Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

Tomé‐Carneiro

Larrosa²,

González‐Sarrías

et al. 2013

CPD

397

294

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Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of food-stuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. In line with this expectation, many resveratrol-based nutraceuticals are consumed all over the world with questionable clinical/scientific support. In fact, the confirmation of these benefits in humans through randomized clinical trials is still very limited. The vast majority of preclinical studies have been performed using assay conditions with a questionable extrapolation to humans, i.e. too high concentrations with potential safety concerns (adverse effects and drug interactions), short-term exposures, in vitro tests carried out with non-physiological metabolites and/or concentrations, etc. Unfortunately, all these hypothesis-generating studies have contributed to increased the number of ‘potential’ benefits and mechanisms of resveratrol but confirmation in humans is very limited. Therefore, there are many issues that should be addressed to avoid an apparent endless loop in resveratrol research. The so-called ‘Resveratrol Paradox’, i.e., low bioavailability but high bioactivity, is a conundrum not yet solved in which the final responsible actor (if any) for the exerted effects has not yet been unequivocally identified. It is becoming evident that resveratrol exerts cardioprotective benefits through the improvement of inflammatory markers, atherogenic profile, glucose metabolism and endothelial function. However, safety concerns remain unsolved regarding chronic consumption of high RES doses, specially in medicated people. This review will focus on the currently available evidence regarding resveratrol’s effects on humans obtained from randomized clinical trials. In addition, we will provide a critical outlook for further research on this molecule that is evolving from a minor dietary compound to a possible multi-target therapeutic drug.

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Section: Preclinical Studiesmentioning

confidence: 81%

Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

Tomé‐Carneiro

Larrosa²,

González‐Sarrías

et al. 2013

CPD

397

294

View full text Add to dashboard Cite

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“…Resveratrol is known to have both cardioprotective and antitumor activities [7,18] and it can attenuate DOX-induced early cellular damage in cancer patients [19]. Thus RSVL is a perfect candidate to be used as a sensitizing agent to modulate the cytotoxic effect of DOX against the growth of breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer cell line

Osman¹,

Bayoumi²,

Al-Harthi³

et al. 2012

Cancer Cell Int

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BackgroundBreast cancer is the most common cancer in the Arab world and it ranked first among Saudi females. Doxorubicin (DOX), an anthracycline antibiotic is one of the most effective anticancer agents used to treat breast cancer. chronic cardiotoxicity is a major limiting factor of the use of doxorubicin. Therefore, our study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of human breast cancer cells (MCF-7) to the action of DOX in an attempt to minimize doxorubicin effective dose and thereby its side effects.MethodsHuman breast cancer cell line MCF-7, was used in this study. Cytotoxic activity of DOX was determined using (sulforhodamine) SRB method. Apoptotic cells were quantified after treatment by annexin V-FITC- propidium iodide (PI) double staining using flow-cytometer. Cell cycle disturbance and doxorubicin uptake were determined after RSVL or DOX treatment.ResultsTreatment of MCF-7 cells with 15 μg/ml RSVL either simultaneously or 24 h before DOX increased the cytotoxicity of DOX, with IC50 were 0.056 and 0.035 μg/ml, respectively compared to DOX alone IC50 (0.417 μg/ml). Moreover, flow cytometric analysis of the MCF-7 cells treated simultaneously with DOX (0.5 μg/ml) and RSVL showed enhanced arrest of the cells in G0 (80%). On the other hand, when RSVL is given 24 h before DOX although there was more increased in the cytotoxic effect of DOX against the growth of the cells, however, there was decreased in percentage arrest of cells in G0, less inhibition of DOX-induced apoptosis and reduced DOX cellular uptake into the cells.ConclusionRSVL treatment increased the cytotoxic activity of DOX against the growth of human breast cancer cells when given either simultaneously or 24 h before DOX.

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“…RES has numerous protective features; it can reduce the risk of cardiovascular disease and protect cardiomyocytes from apoptosis (25). It has also been demonstrated to protect cardiomyocytes against DOX-induced apoptosis (26). In addition, RES has been shown to enhance the anti-cancer activity of DOX, and protect against DOX-induced cardiac toxicity in vitro and in mice (11).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol inhibits doxorubicin-induced cardiotoxicity via sirtuin 1 activation in H9c2 cardiomyocytes

Liu

Shan

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Doxorubicin (DOX) is an efficient drug used in cancer therapy; however, it can induce severe cytotoxicity, which limits its clinical application. In the present study, the effects of resveratrol (RES) on sirtuin 1 (SIRT1) activation in mediating DOX-induced cytotoxicity in H9c2 cardiac cells was investigated. H9c2 cells were exposed to 5 µM DOX for 24 h to establish a model of DOX cardiotoxicity. Apoptosis of H9c2 cardiomyocytes was assessed using the MTT assay and Hoechst nuclear staining. The results demonstrated that pretreating H9c2 cells with RES prior to the exposure of DOX resulted in increased cell viability and a decreased quantity of apoptotic cells. Western blot analysis demonstrated that DOX decreased the expression level of SIRT1. These effects were significantly alleviated by co-treatment with RES. In addition, the results demonstrated that DOX administration amplified forkhead box O1 (FoxO1) and P53 expression levels in H9c2 cells. RES was also found to protect against DOX-induced increases of FoxO1 and P53 expression levels in H9c2 cells. Furthermore, the protective effects of RES were arrested by the SIRT1 inhibitor nicotinamide. In conclusion, the results demonstrated that RES protected H9c2 cells against DOX-induced injuries via SIRT1 activation.

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Resveratrol attenuates doxorubicin-induced cellular damage by modulating nitric oxide and apoptosis

Cited by 69 publications

References 37 publications

Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

Modulation of doxorubicin cytotoxicity by resveratrol in a human breast cancer cell line

Resveratrol inhibits doxorubicin-induced cardiotoxicity via sirtuin 1 activation in H9c2 cardiomyocytes

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