Structure Identification of ViceninII Extracted from Dendrobium officinale and the Reversal of TGF-β1-Induced Epithelial–Mesenchymal Transition in Lung Adenocarcinoma Cells through TGF-β/Smad and PI3K/Akt/mTOR Signaling Pathways

Abstract

ViceninII is a naturally flavonoid glycoside extracted from Dendrobium officinale, a precious Chinese traditional herb, has been proven to be valuable for cancer treatment. Transforming growth factor-β1 (TGF-β1), promotes the induction of epithelial–mesenchymal transition (EMT), a process involved in the metastasis of cells that leads to enhanced migration and invasion. However, there is no previously evidence that ViceninII has an inhibitory effect on cancer metastasis, specifically on the TGF-β1-induced EMT process in lung adenocarcinoma cells. In this experiment, we used UV, ESIMS, and NMR to identify the structure of ViceninII.A549 and H1299 cells were treated with TGF-β1 in the absence and presence of ViceninII, and subsequent migration and invasion were measured by wound-healing and transwell assays. The protein localization and expressions were detected by immunofluorescence and Western blotting. The results indicated that TGF-β1 induced spindle-shaped changes, increased migration and invasion, and upregulated or downregulated the relative expression of EMT biomarkers. Meanwhile, these alterations were significantly inhibited when co-treated with ViceninII and inhibitors LY294002 and SB431542. In conclusion, ViceninII inhibited TGF-β1-induced EMT via the deactivation of TGF-β/Smad and PI3K/Akt/mTOR signaling pathways.This is the first time that the anti-metastatic effects of ViceninII have been demonstrated, and their molecular mechanisms provided.

STRIP2, a member of the striatin‐interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration

“…Through targeting the PI3K/Akt pathway, CNTN-1 boosted chemoresistance in LUAD via abduction of EMT [21]. Studies have indicated that the expression levels of some vital factors (such as E-cadherin, Ncadherin, Vimentin and MMP-9) have been detected during the process of EMT [22,23]. As reported, Ecadherin is a suppressor, whereas N-cadherin, Vimentin and MMP-9 are promoters [24,25].…”

Transforming Growth Factor-β: A Multifunctional Regulator of Cancer Immunity

“…Meanwhile, the TGF-β/Smad pathway also has a negative feedback mechanism mediated through Smad7 competitive binding to TGFBR1 and blocking the TGF-β/Smad pathway signalling [ 10 ]. For the non-canonical TGF-β pathway, the activated TGF-β crosstalks with other signalling pathways, such as Rho, phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) signalling cascades, to promote EMT [ 11 ], cancer invasion [ 12 ], and angiogenesis [ 13 ]. In consequence, both the canonical and non-canonical TGF-β pathways play an important role in cancer progression [ 14 ].…”

Functional analysis of a novel C-glycosyltransferase in the orchid Dendrobium catenatum

“…C-glycosylflavones are critical in plant physiology and are beneficial for human health. For example, vicenin-2 is an effective flavone that shows anti-inflammatory 6 , antiglycating 7 , antispasmodic 8 , antiseptic 9 , antiplatelet, antithrombotic 10 , and anticancer 11,12 activity. Because flavonoids show such high biological activity, determining the pathways involved in the biosynthesis of flavonoid glycosides is important.…”