Andrographolide impedes cancer stemness and enhances radio-sensitivity in oral carcinomas via miR-218 activation

Yang, Po-Yu; Hsieh, Pei‐Ling; Wang, Tong Hong; Yu, Cheng–Chia; Lu, Michael S.-C.; Liao, Yi-Wen; Lee, Tzu-Hsin; Peng, Cheng-Ming

doi:10.18632/oncotarget.13755

Cited by 52 publications

(41 citation statements)

References 62 publications

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“…Cell protein extraction was performed as previously described . The sample was separated on 10% SDS‐PAGE and transferred to polyvinylidene difluoride membrane (Amersham, Arlington Heights, Illinois).…”

Section: Methodsmentioning

confidence: 99%

Hinokitiol ablates myofibroblast activation in precancerous oral submucous fibrosis by targeting Snail

Yang

Chiu

et al. 2018

Environmental Toxicology

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Oral submucous fibrosis (OSF) is a precancerous condition with symptoms of limited mouth opening and areca nut chewing habit has been implicated in its pathogenesis. Hinokitiol, a natural tropolone derived from Chamacyparis taiwanensis, has been reported to improve oral lichen planus and inhibit various cancer cells. Here, we showed that hinokitiol reduced the myofibroblast activities in fBMFs and prevented the arecoline-induced transdifferentiation. Treatment of hinokitiol dose-dependently downregulated the myofibroblast markers as well as various EMT transcriptional factors. In particular, we identified that Snail was able to bind to the E-box in the α-SMA promoter. Our data suggested that exposure of fBMFs to hinokitiol mitigated the hallmarks of myofibroblasts, while overexpression of Snail eliminated the effect of hinokitiol. These findings revealed that the inhibitory effect of hinokitiol on myofibroblasts was mediated by repression of α-SMA via regulation of Snail and showed the anti-fibrotic potential of hinokitiol in the treatment of OSF.

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Section: Methodsmentioning

confidence: 99%

Hinokitiol ablates myofibroblast activation in precancerous oral submucous fibrosis by targeting Snail

Yang

Chiu

et al. 2018

Environmental Toxicology

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“…Western blot analysis was conducted as previously described . The primary antibodies against COL1A1, α‐SMA, phosph‐Smad2 and Smad2 were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Glabridin inhibits the activation of myofibroblasts in human fibrotic buccal mucosal fibroblasts through TGF‐β/smad signaling

Lee

Chu

Hsieh

et al. 2017

Environmental Toxicology

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Oral submucous fibrosis (OSF) has been recognized as one of the oral potentially malignant disorders. Areca nut chewing is implicated in this pathological fibrosis, and it causes chronic inflammation and persistent activation of myofibroblasts. As yet, existing treatments only provide temporary symptomatic relief and there is a lack of an effective intervention to cure OSF. Therefore, development of approaches to ameliorate myofibroblast activities becomes a crucial objective to prevent the malignant progression of OSF. In this study, we examined the inhibitory effect of glabridin, an isoflavane extracted from licorice root, on the myofibroblast characteristics in human fibrotic buccal mucosal fibroblasts (fBMFs). Our results showed that myofibroblast activities, including collagen gel contractility, migration, invasion and wound healing abilities were reduced after exposure of glabridin in a dose-dependent manner. Most importantly, we demonstrated that the arecoline-induced myofiroblast activities were abolished by glabridin treatment. Additionally, the expression of the myofibroblast marker α-smooth muscle actin and other fibrogenic marker, type I collagen, in fBMFs were dose-dependently downregulated. Moreover, we showed that the production of TGF-β was suppressed by glabridin in fBMFs and the protein expression of phospho-Smad2 was decreased as well. In summary, our data suggested that glabridin repressed the myofibroblast features in fBMFs via TGF-β/Smad2 signaling pathway. Glabridin also prevented the arecoline-increased myofibroblast activities, and could serve as a natural anti-fibrosis compound for OSF.

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“…Cell migration assay was conducted using 24‐well plate Transwell ® system with a polycarbonate filter membrane of 8‐μm pore size (Corning, Acton, MA, USA) assay kit as previously described . The migrated cancer cells were then visualized and counted from 5 randomly selected fields under 100‐fold magnification using an inverted microscope.…”

Section: Methodsmentioning

confidence: 99%

miR‐200b ameliorates myofibroblast transdifferentiation in precancerous oral submucous fibrosis through targeting ZEB2

Liao

Hsieh

et al. 2018

J Cellular Molecular Medi

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Oral submucous fibrosis (OSF) is a progressive scarring disease. MicroRNA‐200b (miR‐200b) has been reported as a tumour suppressor, but its role in the precancerous OSF remains unknown. In this study, we investigated the impact of miR‐200b on myofibroblastic differentiation activity. Arecoline is a major areca nut alkaloid and has been employed to induce the elevated myofibroblast activity in human buccal mucosal fibroblasts (BMFs). Treatment of arecoline in BMFs dose‐dependently reduced gene expression of miR‐200b, which corresponded with the decreased expression of miR‐200b in fBMFs. The arecoline‐induced myofibroblast activities were abolished by overexpression of miR‐200b in BMFs, and the same results were observed in fBMFs. In addition, α‐SMA was inhibited by an increase in miR‐200b. We further demonstrated that miR‐200b‐mediated decrease in ZEB2 led to down‐regulation of α‐SMA, vimentin. Loss of miR‐200b resulted in enhanced collagen contraction and migration capabilities, and knockdown of ZEB2 reversed these phenomena. Lastly, we showed the expression of miR‐200b was significantly less and ZEB2 was markedly higher in OSF tissues. These results suggested that down‐regulation of miR‐200b may contribute to the pathogenesis of areca quid‐associated OSF through the regulation of ZEB2 and myofibroblast hallmarks.

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Andrographolide impedes cancer stemness and enhances radio-sensitivity in oral carcinomas via miR-218 activation

Cited by 52 publications

References 62 publications

Hinokitiol ablates myofibroblast activation in precancerous oral submucous fibrosis by targeting Snail

Hinokitiol ablates myofibroblast activation in precancerous oral submucous fibrosis by targeting Snail

Glabridin inhibits the activation of myofibroblasts in human fibrotic buccal mucosal fibroblasts through TGF‐β/smad signaling

miR‐200b ameliorates myofibroblast transdifferentiation in precancerous oral submucous fibrosis through targeting ZEB2

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