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Lipopolysaccharide Attenuates the Cytotoxicity of Resveratrol in Transformed Mouse Macrophages

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Abstract

Resveratrol and pterostilbene are natural products that are present in plants and have been incorporated into various dietary supplements. Numerous beneficial pharmacologic effects have been reported for these stilbenes; however, the mechanism by which these compounds exert a cytotoxic effect in RAW 264.7 macrophages has not been well characterized. We have previously described that resveratrol is toxic to these tumor-derived macrophages and that stimulation with lipopolysaccharide (LPS) reduces resveratrol toxicity via a mechanism that involves activation of toll like receptor 4. In the present work, we examined the cellular and molecular effects of resveratrol and the related compound pterostilbene by determining cell viability and caspase 3 activity in control and LPS-stimulated RAW 264.7 macrophages incubated with these stilbenes for 24 h. We found that LPS stimulation reduced the cytotoxicity of resveratrol but not of pterostilbene in these cells. When examined for effects on caspase 3 activation after a 24 h incubation, resveratrol and pterostilbene were each found to separately and significantly increase caspase 3 activity in these cells. LPS stimulation prevented caspase 3 activation by pterostilbene and reduced caspase 3 activation by resveratrol in RAW 264.7 macrophages. The data presented here indicate that LPS induces a phenotype switch in tumor-derived RAW 264.7 macrophages in which cells experiencing LPS in the presence of resveratrol or pterostilbene become less likely to activate the pro-apoptotic factor caspase 3.

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Abbreviations

DMEM:

Dulbecco’s Modified Eagle’s Medium

DMSO:

dimethylsulfoxide

LPS:

lipopolysaccharide

MTT:

3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide

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Acknowledgments

The authors thank the Department of Pharmaceutical Sciences for providing the funding for these experiments.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, 8000 Utopia Parkway, Jamaica, NY, 11439, USA

    Christelle A. Adiabouah Achy-Brou & Blase Billack

Authors
  1. Christelle A. Adiabouah Achy-Brou
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  2. Blase Billack
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Correspondence to Blase Billack.

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The authors declare that there are no conflicts of interest.

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Achy-Brou, C.A.A., Billack, B. Lipopolysaccharide Attenuates the Cytotoxicity of Resveratrol in Transformed Mouse Macrophages. Plant Foods Hum Nutr 71, 272–276 (2016). https://doi.org/10.1007/s11130-016-0556-3

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