Suppression of Transforming Growth Factor Beta/Smad Signaling in Keloid-Derived Fibroblasts by Quercetin: Implications for the Treatment of Excessive Scars

Phan, Toan Thang; Lim, Ivor J.; Chan, Sui Yung; Tan, Edwin T.; Lee, Seng-Teik; Longaker, Michael T.

doi:10.1097/01.ta.0000114087.46566.eb

Cited by 93 publications

(70 citation statements)

References 33 publications

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“…In the case of quercetin this outcome was not found to be true and quercetin significantly added to the inhibitory action of TNFα, rather than alleviating it. Although unexpected, our data are consistent with a previous report in which quercetin inhibited Smad activation in keloid-derived fibroblasts (33).…”

Section: Discussionsupporting

confidence: 93%

Quercetin, a potent suppressor of NF-κB and Smad activation in osteoblasts

Weitzmann¹

2011

Int J Mol Med

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Abstract. Osteoclasts, the bone resorbing cells of the body, form when osteoclast precursors are exposed to the key osteoclastogenic cytokine receptor activator of NF-κB ligand (RANKL), a process requiring induction of NF-κB signaling. Quercetin is a ubiquitous plant-derived flavonoid with well documented antiinflammatory properties, in part, a consequence of its capacity to downmodulate the NF-κB signal transduction pathway. Consistent with this mechanism of action quercetin is reported to suppress osteoclastogenesis in vitro and prevent bone loss in ovariectomized mice in vivo. By contrast, the effect of quercetin on osteoblasts, the cells responsible for bone formation, is contradictory with conflicting reports of inhibition as well as stimulation. Given our previous reports that NF-κB antagonists promote osteoblast differentiation and activity, we compared the effects of quercetin on osteoclast and osteoblast differentiation and on NF-κB signal transduction in vitro. As expected, quercetin potently suppressed osteoclastogenesis and NF-κB activation induced by RANKL in osteoclast precursors. However, the same doses of quercetin had no effect on osteoblast mineralization, and failed to significantly alleviate the inhibitory effect of NF-κB-induced by TNFα, even though quercetin potently suppressed NF-κB activation in these cells. This apparent contradiction was explained by the fact that addition to its anti-NF-κB activity, quercetin also potently antagonized both TGFβ and BMP-2-induced Smad activation in osteoblast precursors. Taken together our data suggest that multiple competing actions of quercetin mediate both stimulatory and inhibitory actions on osteoblasts with the final physiological effect likely a function of the net balance between these stimulatory and inhibitory effects.

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Section: Discussionsupporting

confidence: 93%

Quercetin, a potent suppressor of NF-κB and Smad activation in osteoblasts

Weitzmann¹

2011

Int J Mol Med

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“…Quercetin is a naturally occurring dietary flavenoid (available as an over-the-counter supplement) that functions both as an MCT/ lactate transport inhibitor and inhibitor of TGFbeta signaling. [50][51][52] One explanation for these dual activities is that L-lactate uptake into tumor cells somehow metabolically activates TGFbeta signaling. As such, the inhibitory effects of quercetin on TGFbeta signaling may be due to its ability to inhibit the uptake of L-lactate into tumor cells, presumably resulting in reduced cell migration and metastasis.…”

Section: Methodsmentioning

confidence: 99%

Ketones and lactate “fuel” tumor growth and metastasis

Bonuccelli¹,

Tsirigos²,

et al. 2010

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“…Quercetin, a strong dietary antioxidant, was found to inhibit Wnt/bcatenin signalling in SW480 colon cancer cells [21] and growth in acute lymphoblastic leukaemia cell lines [22]. Our group previously reported the inhibition of KFs' growth by quercetin through the suppression of insulin growth factor (IGF)-1 [23] and TGF-b [24] signalling pathways. It would therefore be interesting to determine if quercetin acts on the Wnt/b-catenin signalling as well.…”

Section: Introductionmentioning

confidence: 99%