Curcumol induces HSC-T6 cell death through suppression of Bcl-2: Involvement of PI3K and NF-κB pathways

Chen, Gang; Wang, Yinghang; Li, Meiqian; Xu, Tianjiao; Wang, Xiaoli; Bao, Hong; Niu, Yingcai

doi:10.1016/j.ejps.2014.09.001

Cited by 47 publications

(33 citation statements)

References 30 publications

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“…36 Studies have demonstrated NF-κB inhibition promotes HSC-T6 cell death via Bcl-2 suppression. 37,38 Our finding were consistent with those of Jeong and colleagues who showed that Agn inhibits NF-κB. 39 We further showed that Agn inhibits p65 and IκBα phosphorylation.…”

Section: Discussionsupporting

confidence: 90%

<p>Alginate Suppresses Liver Fibrosis Through the Inhibition of Nuclear Factor-κB Signaling</p>

Xia¹,

Ding²,

Zheng³

et al. 2020

DDDT

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Purpose: Liver fibrosis (or liver scarring) is a causative factor for hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Alginate (Agn) isolated from brown algae is known to slow the proliferation of fibroblasts, through the mechanisms of these effects remain undefined. This study explored the benefits of Agn on hepatic health and its associated mechanism(s) of action in hepatic stellate cells (HSC-T6s). Materials and Methods: To assess the effects of Agn, HSC-T6s were treated with PDGF and cell proliferation, colony formation, cell migration, cell invasiveness and apoptosis were assessed. Rat models of liver fibrosis were produced through 12-week injections of intraperitoneal (IP) carbon tetrachloride (CCl 4 ). Rats were Agn-treated from weeks 8 to 12, and liver damage was assessed through Masson's and H Materials and Methods: & E staining. Gene expression profiles were assayed via RT-PCR, Western blot and commercial ELISA kits. Results: Agn reduced the proliferation of HSC-T6s and increased apoptotic rates through the downregulation of the Bcl-2:Bax ratio. Agn also inhibited the invasion and migration of HSC-T6s, prevented ECM deposition, and reduced the occurrence of liver fibrosis in rat models. Agn also prevented IκBα and p65 phosphorylation. Conclusion: Agn prevents liver fibrosis through its attenuation of HSC activation and division through the suppression of NF-κB in in vitro and animal models. This highlights how the clinical use of Agn can prevent hepatic fibrosis.

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Section: Discussionsupporting

confidence: 90%

<p>Alginate Suppresses Liver Fibrosis Through the Inhibition of Nuclear Factor-κB Signaling</p>

Xia¹,

Ding²,

Zheng³

et al. 2020

DDDT

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“…24,25 Meanwhile, curcumol also exhibited different effects on ROS in previous reports. 26,27 Although we do not provide direct evidence, the speculation is that curcumol's suppression of JNK1/2 and Akt activity may be related to ROS, and more specific studies are needed to directly address this question.…”

Section: Discussionmentioning

confidence: 92%

Curcumol Suppresses Breast Cancer Cell Metastasis by Inhibiting MMP-9 Via JNK1/2 and Akt-Dependent NF-κB Signaling Pathways

Ning

Jiang

et al. 2016

Integr Cancer Ther

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Curcumolhas been reported to possess antitumor activity. However, its effect and mechanisms against tumor metastasis are still unclear. This study is to investigate the inhibitory effect of curcumol on breast cancer cell metastasis and elucidate the underlying molecular mechanisms. Our results showed that noncytotoxicity was caused by curcumol within 10 to 40 µg/mL in MDA-MB-231 and 4T1 cells for 24 hours, whereas sustained treatment with curcumol for 14 days significantly suppressed the clonogenic activity of cells. Importantly, curcumol at noncytotoxic concentrations suppressed the migration ability of both MDA-MB-231 and 4T1 cells. Moreover, curcumol suppressed the migration and invasion of MDA-MB-231 cells in the Boyden chamber migration and invasion assay and inhibited the adhesion of MDA-MB-231 cells onto the matrigel. Further investigations revealed that curcumol decreased the enzyme activity and protein expression of matrix metalloproteinase (MMP-9) in MDA-MB-231 cells. Moreover, curcumol inhibited the activation of c-Jun N-terminal kinase (JNK) 1/2 and Akt (Ser473). Meanwhile, it also inhibited the nuclear translocation and transcriptional activity of nuclear factor κB (NF-κB). Furthermore, JNK inhibitor SP600125 and Akt (Ser473) inhibitor LY294002 enhanced the inhibition of curcumol on NF-κB p65 nuclear translocation. Finally, supplementation with SP600125, LY294002, or NF-κB inhibitor Ammonium pyrrolidinedithiocarbamate (PDTC) significantly enhanced the inhibitory effect of curcumol on MMP-9 expression and cell migration, invasion, and adhesion in MDA-MB-231 cells. Our findings provide evidence for the suppression of breast cancer cell metastasis by curcumol and suggest that the inhibition of MMP-9 via JNK1/2 and Akt (Ser473)-dependent NF-κB signaling pathways may be the underlying mechanisms.

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“…Thus, emodin‐mediated inhibition of HSCs activation, indicated by α‐SMA, type I collagen, and fibronectin, in vitro simulated the results of our previous in vivo studies (M. X. Dong et al, ). Increasing evidence suggests that the elimination of activated HSCs through apoptosis has been proposed as a therapeutic antifibrogenic strategy (G. Chen et al, ). In the present study, we found that treatment of HSC‐T6 cell with emodin led to only a marginal apoptotic response whereas no significant changes occurred in LDH release.…”

Section: Discussionmentioning

confidence: 99%

Emodin suppresses activation of hepatic stellate cells through p38 mitogen‐activated protein kinase and Smad signaling pathways in vitro

Wang

Niu

Zhang

et al. 2018

Phytotherapy Research

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The aim of this study was to evaluate the hypothesis that emodin inhibits extracellular matrix (ECM)-related gene expression in activated hepatic stellate cells (HSCs) by blocking canonical or/and noncanonical components of transforming growth factor β1 (TGFβ1) intracellular signaling. Here, we demonstrate that emodin suppressed the gene expression of HSCs activation markers type I collagen, fibronectin, and α-smooth muscle actin, as well as HSCs proliferation. Mechanistically, emodin suppresses TGFβ1, TGFβ receptor II, TGFβ receptor I, and Smad4 gene expression, as well as Smad luciferase activity. Simultaneously, emodin reduced p38 mitogen-activated protein kinase (p38 ) activity but not c-Jun N-terminal kinases and extracellular signal-regulated kinases 1 and 2 phosphorylation in HSC-T6 cells. Interestingly, deprivation of TGFβ using a neutralizing antibody abolished emodin-mediated inhibitions of the both Smad transcriptional activity and p38 phosphorylation. Furthermore, emodin-mediated inhibition of HSCs activation could be partially blocked by PD98059 inhibition of p38 or short hairpin RNA-imposed knockdown of Smad4. Conversely, simultaneous inhibition of Smad4 and p38 pathways completely reverses the effects of emodin, suggesting that Smad and p38 locate downstream of TGFβ1 and regulate collagen genes expression in HSCs. Collectively, these data suggest that emodin is a promising candidate for the treatment of hepatic fibrosis.

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Curcumol induces HSC-T6 cell death through suppression of Bcl-2: Involvement of PI3K and NF-κB pathways

Cited by 47 publications

References 30 publications

<p>Alginate Suppresses Liver Fibrosis Through the Inhibition of Nuclear Factor-κB Signaling</p>

<p>Alginate Suppresses Liver Fibrosis Through the Inhibition of Nuclear Factor-κB Signaling</p>

Curcumol Suppresses Breast Cancer Cell Metastasis by Inhibiting MMP-9 Via JNK1/2 and Akt-Dependent NF-κB Signaling Pathways

Emodin suppresses activation of hepatic stellate cells through p38 mitogen‐activated protein kinase and Smad signaling pathways in vitro

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