Luteolin affects keloid fibroblast proliferation and apoptosis by regulating FRAT1 gene expression

Abstract

The current experiment was performed to investigate whether luteolin affects the proliferation and apoptosis of keloid fibroblasts by regulating the expression of FRAT1 gene. Keloid fibroblasts were treated with luteolin at different concentrations. MTT method, western blot, flow cytometry, and real-time quantitative PCR (qPCR) were used to detect cell proliferation, cyclin D1 (CyclinD1), p21, B-cell lymphoma / leukemia-2 (Bcl-2), Bcl-2 related X protein (Bax), FRAT1 protein expression, apoptosis and ARHI mRNA expression. Keloid fibroblasts were transfected with si-FRAT1, or pcDNA-FRAT1 and treated with luteolin to observe their roles in cell proliferation and apoptosis. Compared with the control group, luteolin significantly reduced the keloid fibroblast activity, CyclinD1, Bcl-2, and FRAT1 protein levels, and obviously improved the cell apoptosis rate, p21 and Bax protein expression (P<0.05). The expression of FRAT1 mRNA and protein in keloid fibroblasts was greatly increased (P<0.05). Inhibition of FRAT1 expression evidently decreased cell viability at 24 h, 48 h, and 72 h, CyclinD1, and Bcl-2 protein expression of keloid fibroblasts, while-dramatically enhanced cell apoptosis, p21, and Bax protein levels (P<0.05). FRAT1 overexpression reversed the inhibitory effect of luteolin on keloid fibroblast activity, FRAT1, CyclinD1, and Bcl-2 protein expression, and promotion of apoptosis, p21 and Bax protein expression. Luteolin can inhibit the proliferation and induce apoptosis of keloid fibroblasts by regulating the expression of FRAT1 gene.

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“…Luteolin decreased the KF viability and the expression levels of cyclin D1, BCL-2, and FRAT1, and increased cell apoptosis, p21, and BAX expression [113]. The pro-apoptotic effects of luteolin were abolished by overexpressed FRAT1, a GSKβ3 inhibitor causing β-catenin activation in the Wnt signaling pathway, and siRNA-mediated FRAT1 depletion increased cell apoptosis [113].…”

“…Their potential mechanisms of action for inducing cell cycle arrest or apoptosis are summarized in Figure 4. Luteolin inhibits the Wnt signaling pathway by promoting the degradation of βcatenin by downregulating FRAT1, which inhibits the GSK3β-mediated phosphorylation of β-catenin [113]. As a result, luteolin induces cell cycle arrest or apoptosis, which is associated with low levels of cyclin D1 and BCL-2 and high levels of p21 and BAX [113].…”

“…PDT with hypocrellin A increases ROS production and apoptosis by upregulating BAX and caspase-3. Se-ZGTP induces apoptosis, which is accompanied by a decrease in BCL-2 and increases in BAX and caspase-3, and the subsequent cleavage and inactivation of PARP that mediates the Luteolin inhibits the Wnt signaling pathway by promoting the degradation of βcatenin by downregulating FRAT1, which inhibits the GSK3β-mediated phosphorylation of β-catenin [113]. As a result, luteolin induces cell cycle arrest or apoptosis, which is associated with low levels of cyclin D1 and BCL-2 and high levels of p21 and BAX [113].…”

“…Se-ZGTP induces apoptosis, which is accompanied by a decrease in BCL-2 and increases in BAX and caspase-3, and the subsequent cleavage and inactivation of PARP that mediates the Luteolin inhibits the Wnt signaling pathway by promoting the degradation of βcatenin by downregulating FRAT1, which inhibits the GSK3β-mediated phosphorylation of β-catenin [113]. As a result, luteolin induces cell cycle arrest or apoptosis, which is associated with low levels of cyclin D1 and BCL-2 and high levels of p21 and BAX [113]. Wubeizi ointment induces cell cycle arrest by increasing phosphatase and tensin homolog (PTEN) through the downregulation of miR-21 [96][97][98][99], which results in the inhibition of the AKT/mTOR pathway.…”