Concentration-Dependent Biphasic Effects of Resveratrol on Human Natural Killer Cells<i>in Vitro</i>

Li, Qi; Huyan, Ting; Ye, Lin-Jie; Ji, Li; Shi, Junling; Huang, Qingsheng

doi:10.1021/jf502950u

Cited by 39 publications

(32 citation statements)

References 43 publications

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“…[421] showed that in vitro exposure to resveratrol produced a biphasic effect on anti-CD3/anti-CD28-induced development of both IFN-γ - IL2- and IL4-producing CD8+ and CD4+ T cells (with stimulation at low resveratrol concentrations and suppression at high concentrations). Similarly, it was found to induce a significant enhancement at low concentrations and suppression at high concentrations of both cytotoxic T lymphocytes and NK cell cytotoxic activity [421], and this biphasic modulation of NK cells has been confirmed in more recent research as well [422]. The administration of low doses of resveratrol also inhibited Renca tumor growth with regulatory T cells being decreased, and a massive amount of activated CD8 + T cells accumulating in the tumor microenvironment.…”

Section: Low Toxicity Approachesmentioning

confidence: 79%

A multi-targeted approach to suppress tumor-promoting inflammation

Samadi

Bilsland

Georgakilas

et al. 2015

Seminars in Cancer Biology

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Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.

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Section: Low Toxicity Approachesmentioning

confidence: 79%

A multi-targeted approach to suppress tumor-promoting inflammation

Samadi

Bilsland

Georgakilas

et al. 2015

Seminars in Cancer Biology

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“…RES concentrations of 25 and 50 µM diminished NK cells cytotoxicity by 29% and 39%, respectively. At 3.13 µM RES was demonstrated to enhance the expression of both TNFγ (by 4.5-fold) and triggering cytotoxicity receptor NKG2D (by 6.4-fold), which might account for the enhanced cytotoxicity of NK cells [59].…”

Section: Resveratrolmentioning

confidence: 94%

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Jodynis‐Liebert

Kujawska

2020

JCM

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Many phytochemicals demonstrate nonmonotonic dose/concentration-response termed biphasic dose-response and are considered to be hormetic compounds, i.e., they induce biologically opposite effects at different doses. In numerous articles the hormetic nature of phytochemicals is declared, however, no experimental evidence is provided. Our aim was to present the overview of the reports in which phytochemical-induced biphasic dose-response is experimentally proven. Hence, we included in the current review only articles in which the reversal of response between low and high doses/concentrations of phytochemicals for a single endpoint was documented. The majority of data on biphasic dose-response have been found for phytoestrogens; other reports described these types of effects for resveratrol, sulforaphane, and natural compounds from various chemical classes such as isoquinoline alkaloid berberine, polyacetylenes falcarinol and falcarindiol, prenylated pterocarpan glyceollin1, naphthoquinones plumbagin and naphazarin, and panaxatriol saponins. The prevailing part of the studies presented in the current review was performed on cell cultures. The most common endpoint tested was a proliferation of tumor and non-cancerous cells. Very few experiments demonstrating biphasic dose-response induced by phytochemicals were carried out on animal models. Data on the biphasic dose-response of various endpoints to phytochemicals may have a potential therapeutic or preventive implication.

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“…However, in this study, PO-MSC viability decreased when resveratrol dose was above 10 μM. It seems that the osteogenic effect of resveratrol varies according to dosage or cell types (33)(34)(35)(36)(37). Therefore, further investigation on the optimal dosage and administration method of resveratrol for accelerating osteogenesis of PO-MSC is needed.…”

Section: Discussionmentioning

confidence: 63%

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

Moon

Kim

Lee

et al. 2020

Preprint

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Background: Osteoporosis is a metabolic bone disorder that leads to low bone mass and microstructural deterioration of bone tissue and increases bone fractures. Resveratrol, a natural polyphenol compound, has pleiotropic effects including anti-oxidative, anti-aging, and anti-cancer effects. Resveratrol also has roles in increasing osteogenesis and in up-regulating mitochondrial biogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, it is still unclear that resveratrol can enhance osteogenic differentiation or mitochondrial biogenesis of periosteum-derived MSCs (PO-MSCs), which play key roles in bone tissue maintenance and fracture healing. Thus, in order to test a possible preventive or therapeutic effect of resveratrol on osteoporosis, this study investigated effects of resveratrol treatments on osteogenic differentiation and mitochondrial biogenesis of PO-MSCs.Methods: The optimal doses of resveratrol treatment on PO-MSCs were determined by cell proliferation and viability assays. Osteogenic differentiation of PO-MSCs under resveratrol treatment was assessed by alkaline phosphatase activities (ALP, an early biomarker of osteogenesis) as well as by extracellular calcium deposit levels (a late biomarker). Mitochondrial biogenesis during osteogenic differentiation of PO-MSCs was measured by quantifying both mitochondrial mass and mitochondrial DNA (mtDNA) contents.Results: Resveratrol treatments above 10 µM seem to have negative effects on cell proliferation and viability of PO-MSCs. Resveratrol treatment (at 5 µM) on PO-MSCs during osteogenic differentiation increased both ALP activities and calcium deposits compared to untreated control groups, demonstrating an enhancing effect of resveratrol on osteogenesis. In addition, resveratrol treatment (at 5 µM) during osteogenic differentiation of PO-MSCs increased both mitochondrial mass and mtDNA copy numbers, indicating that resveratrol can bolster mitochondrial biogenesis in the process of PO-MSC osteogenic differentiation.Conclusion: Taken together, the findings of this study describe roles of resveratrol in promoting osteogenesis and mitochondrial biogenesis of human PO-MSCs suggesting a possible application of resveratrol as a supplement for osteoporosis and/or osteoporotic fractures.

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Concentration-Dependent Biphasic Effects of Resveratrol on Human Natural Killer Cellsin Vitro

Cited by 39 publications

References 43 publications

A multi-targeted approach to suppress tumor-promoting inflammation

A multi-targeted approach to suppress tumor-promoting inflammation

Biphasic Dose-Response Induced by Phytochemicals: Experimental Evidence

Resveratrol can enhance osteogenic differentiation and mitochondrial biogenesis from human periosteum-derived mesenchymal stem cells

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