Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPKα and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun

Tang, Qing; Zhao, Shunyu; Wu, Jingjing; Zheng, Fang; Yang, Lijun; Hu, JingHeng; Hann, Swei Sunny

doi:10.1016/j.cellsig.2015.04.005

Cited by 41 publications

(32 citation statements)

References 47 publications

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“…We previously demonstrated that emodin inhibited multiple NSCLC cell proliferation as determined by MTT assays [11]. In the current study, we further defined the role of PPARγ, we showed that emodin-decreased cell viability and -induced cell cycle arrest were not observed in cells with silenced PPARγ gene by siRNA suggesting that activation PPARγ was required in this process (Fig.…”

Section: Resultsmentioning

confidence: 59%

“…We previously demonstrated that emodin reduced specific transcription factor (Sp1) protein expression in A549 and H1975 NSCLC cells [11]. Importantly, we found that the emodin-inhibited Sp1 expression was abrogated in cells with silenced PPARγ gene (Fig.…”

Section: Resultsmentioning

confidence: 60%

“…Consistent with this, we recently found that emodin inhibited growth of NSCLC cells through AMP-activated protein kinase alpha (AMPKα)- and extracellular signaling-regulated kinase (ERK)-mediated inhibition of integrin-linked kinase (ILK) [11]. In addition, one report showed that emodin enhanced chemotherapy-induced cytotoxicity via reducing the expression of excision repair cross-complementation group 1 (ERCC1) in human lung cancer cells [12].…”

Section: Introductionmentioning

confidence: 57%

“…2B). Previously, we found that emodin increased the phosphorylation of ERK1/2 and AMPKα signaling pathways in NSCLC cells [11]. Herein, we showed that the inhibitors of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)⁄ERK (PD98059) and AMPK (compound C) abrogated the effect of emodin (50 µM) on PPARγ protein expression in A549 and H1975 cells (Fig.…”

Section: Resultsmentioning

confidence: 84%

“…We previous showed that emodin inhibited growth of human lung cancer cells [11]. In the current study, we further assessed the relative contribution of inhibition affected by emodin using cell cycle assays.…”

Section: Resultsmentioning

confidence: 99%

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Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Tang¹,

Wu²,

Zheng³

et al. 2017

Cell Physiol Biochem

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Background: Emodin has anti-neoplastic activities on multiple tumors. However, the molecular mechanisms underlying this effect still remain to be fully understood. Methods: Cell viability and cell cycle distribution were measured using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays and flow cytometry, respectively. Cell invasion and migration were examined by transwell invasion and wound healing assays. Western blot analysis was performed to examine the phosphorylation and protein expression of AMP-activated protein kinase alpha (AMPKα), extracellular signaling-regulated kinase 1/2 (ERK1/2), peroxisome proliferators-activated receptor gamma (PPARγ), insulin-like growth factor (IGF) binding protein 1 (IGFBP1) and the transcription factor Sp1. QRT-PCR was used to examine the mRNA levels of the IGFBP1 gene. Small interfering RNAs (siRNAs) were used to knockdown PPARγ and IGFBP1 genes. Exogenously expression of IGFBP1 and Sp1 was determined by transient transfection assays. IGFBP1 promoter activity was measured by Secrete-Pair Dual Luminescence Assay Kit. In vivo nude mice xenograft model and bioluminescent imaging system were used to confirm the findings. Results: We showed that emodin induced cell cycle arrest of NSCLC cells. Emodin increased PPARγ protein and luciferase reporter activity, which were abolished by inhibitors of MAPK extracellular signaling-regulated kinase (ERK) kinase (MEK)/ERK and AMPK. Silencing of PPARγ abrogated emodin-inhibited cell growth and cell cycle arrest. Furthermore, emodin elevated IGFBP1 mRNA, protein, and promoter activity through activation of PPARγ. Intriguingly, overexpressed Sp1 attenuated emodin-induced IGFBP1 expression, which was not observed in cells with silenced PPARγ gene. Moreover, silencing of IGFBP1 gene blunted emodin-induced inhibition of cell growth and cell cycle arrest. On the contrary, overexpressed IGFBP1 enhanced emodin-induced phosphorylation of AMPKα and ERK1/2, and restored emodin-inhibited growth in cells with silenced endogenous IGFBP1 gene. Emodin also inhibited growth of lung xenograft tumors and Sp1, and increased IGFBP1 and PPARγ protein expressions In vivo. Conclusion: Collectively, our results show that emodin inhibits growth of non-small-cell lung cancer (NSCLC) cells through ERK and AMPKα-mediated induction of PPARγ, followed by reduction of Sp1. This in turn induces IGFBP1 gene expression. Thus, the signaling cascades, positive feedback loop and cooperative interplay between transcription factors-induced the expression of IGFBP1 gene contribute to the overall responses of emodin. This study provides a novel mechanism by which emodin inhibits growth of human lung cancer cells.

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Section: Resultsmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

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Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Tang¹,

Wu²,

Zheng³

et al. 2017

Cell Physiol Biochem

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The regulation and interaction of colon cancer‐associated transcript‐1 and miR7‐5p contribute to the inhibition of SP1 expression by solamargine in human nasopharyngeal carcinoma cells

Tang

et al. 2019

Phytotherapy Research

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Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy with higher incidence in Southern China and Southeast Asia. Solamargine (SM), a steroidal alkaloid glycoside, has been shown to have anticancer properties. However, the underlying mechanism involved remains undetermined. In this study, we showed that SM inhibited the growth of NPC cells. Mechanistically, we found that solamargine decreased lncRNA colon cancer-associated transcript-1 (CCAT1) and increased miR7-5p expression. There was a reciprocal interaction of CCAT1 and miR7-5p. In addition, SM inhibited the expression of SP1 protein and promoter activity, which was strengthened by miR7-5p mimics and inhibited by overexpressed CCAT1.MiR7-5p could bind to 3'-UTR of SP1 and attenuated SP1 gene expression. Exogenously expressed SP1 feedback resisted SM-increased miR7-5p expression and more importantly reversed SM-inhibited growth of NPC cells. Finally, SM inhibited NPC tumor growth in vivo. Collectively, our results show that SM inhibits the growth of NPC cells through reciprocal regulation of CCAT1 and miR7-5p, followed by inhibition of SP1 gene expression in vitro and in vivo. The interregulation and correlation among CCAT1, miR7-5p and SP1, and the feedback regulatory loop unveil the novel molecular mechanism underlying the overall responses of SM in anti-NPC.

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Emodin and Its Role in Chronic Diseases

Monisha

Kumar

Tiku

2016

Advances in Experimental Medicine and Biology

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Diseases, such as heart disease, stroke, cancer, respiratory diseases, and diabetes, are by far the leading cause of mortality in the world, representing 60 % of all deaths. Although substantial medical advances have been made and many therapeutic approaches proposed yet traditional medicine and medicinal plants find an important place in therapy. They have been providing invaluable solutions to the various health problems. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a natural anthraquinone derivative found in various Chinese medicinal herbs. Traditionally, it has been used as an active constituent of many herbal laxatives. However, in the last few years, significant progress has been made in studying the biological effects of emodin at cellular and molecular levels and it is emerging as an important therapeutic agent. This review provides an overview of the modulatory effects of emodin in various diseases and cell signaling pathways, which may have important implications in its future clinical use.

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Inhibition of integrin-linked kinase expression by emodin through crosstalk of AMPKα and ERK1/2 signaling and reciprocal interplay of Sp1 and c-Jun

Cited by 41 publications

References 47 publications

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

Emodin Increases Expression of Insulin-Like Growth Factor Binding Protein 1 through Activation of MEK/ERK/AMPKα and Interaction of PPARγ and Sp1 in Lung Cancer

The regulation and interaction of colon cancer‐associated transcript‐1 and miR7‐5p contribute to the inhibition of SP1 expression by solamargine in human nasopharyngeal carcinoma cells

Emodin and Its Role in Chronic Diseases

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