Cellular signaling crosstalk between Wnt signaling and gap junctions inbenzo[a]pyrene toxicity

Won, Dong Hoon; Hwang, Da Bin; Shin, Yoo Sub; Kim, Shin Young; Kim, Changuk; Hong, In Sun; Kang, Byeong Cheol; Hwan, Jeong; Yun, Jun Won

doi:10.1007/s10565-021-09630-z

Cited by 5 publications

(2 citation statements)

References 58 publications

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“…Cx43 is a protein in gap junctions, which are involved in liver damage caused by various drugs, as well as diseases such as liver fibrosis and cirrhosis. 24 Therefore, we determined whether Cx43 expression was altered in the livers of mice treated with oxaliplatin or MgIG. The results showed that oxaliplatin induced the expression of Cx43 in the liver tissue of tumor-bearing mice, and MgIG inhibited the abnormal increase caused by oxaliplatin (p<0.001, Fig.…”

Section: Distribution Of Mgig and Its Metabolite 18 α-Glycyrrhetinic ...mentioning

confidence: 99%

MgIG Attenuates Oxaliplatin-induced Hepatotoxicity through Suppression of Connexin 43 in Hepatic Stellate Cells

Cao¹,

Xia²,

Wang³

et al. 2022

J Clin Transl Hepatol

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Background and Aims:Oxaliplatin is widely used in cancer chemotherapy with adverse effects such as liver toxicity. Magnesium isoglycyrrhizinate (MgIG) has hepatoprotective effects, but the underlying mechanism remains elusive. The study's aim was to investigate the mechanism underlying the hepatoprotective effects of MgIG against oxaliplatin-induced liver injury. Methods: A xenografted colorectal cancer mouse model was established with MC38 cells. Mice were given oxaliplatin (6 mg/kg/week) for 5 weeks to mimic oxaliplatininduced liver injury in vivo. LX-2 human hepatic stellate cell s(HSCs) were employed for in vitro studies. Serological tests, hematoxylin and eosin staining, oil red O staining and transmission electron microscopy were used for histopathological examinations. Real-time PCR, western blotting, immunofluorescence and immunohistochemical staining were used to determine Cx43 mRNA or protein levels. Flow cytometry was used to assay reactive oxygen species (ROS) and mitochondrial membrane. Short hairpin RNA targeting Cx43 was lentivirally transduced in LX-2 cells. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine MgIG and metabolite concentration. Results: MgIG (40 mg/kg/day) treatment significantly reduced serum aspartate transaminase (AST) and alanine transaminase (ALT) levels in the mouse model, and alleviated liver pathological changes, including necrosis, sinusoidal expansion, mitochondrial damage, and fibrosis. MgIG reduced the abnormal expression of Cx43 in the mitochondria and nuclei of HSCs. MgIG inhibited the activation of HSCs via reducing ROS generation, mitochondrial dysfunction, and N-cadherin transcription. MgIG's inhibition of HSCs activation was abolished after knockdown of Cx43 in LX-2 cells. Conclusions: Cx43 mediated MgIG's hepatoprotective effects against ox-

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Section: Distribution Of Mgig and Its Metabolite 18 α-Glycyrrhetinic ...mentioning

confidence: 99%

MgIG Attenuates Oxaliplatin-induced Hepatotoxicity through Suppression of Connexin 43 in Hepatic Stellate Cells

Cao¹,

Xia²,

Wang³

et al. 2022

J Clin Transl Hepatol

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“…GJ channels domain connexin family channel proteins, such as Connexin 43 (Cx43), Cx26, and Cx45, among which Cx43 is the most widely expressed connexin in the majority of tissues and intimately related to amounts of cancer development and metastatic process (Epifantseva & Shaw, 2018). Moreover, there was evidence that Wnt/ β-catenin signal transduction negatively regulates Cx43 expression (Won et al, 2021). Inhibition of Wnt/β-catenin and PI3K/ Akt signaling pathway can promote tumor cell apoptosis (Wang et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Retracted: Connexin 43 upregulation by dioscin‐inhibited gastric cancer metastasis by suppressing PI3K/Akt pathway

Kou

Zhu

Sun

et al. 2022

Food Science & Nutrition

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Dioscin, a natural steroidal saponin isolated from traditional Chinese medicine, is reported to possess antitumor activity against various cancers including gastric cancer (GC). GC patients are commonly found with low expression of Connexin 43 (Cx43) and activated epithelial-mesenchymal transition (EMT). The aim of this study was to investigate the mechanism of dioscin in inhibiting the proliferation, invasion, and metastasis of GC. Cell migration was detected using wound healing analysis while the invasion was used in Transwell membrane chambers. Colony-forming assays were researched for cell potential capacity in proliferation. The data of 68 GC patients treated with radical gastrectomy were collected from 2017 to 2019. The clinicopathological data were recorded for retrospective analysis. Cx43 was measured by immunohistochemistry in GC tissues from patients. EMT-related proteins and PI3K/Akt pathwayassociated proteins were observed by using Western blot analysis. Dioscin inhibited the proliferation, migration, and invasion of SGC-7901 cells. Dioscin increased the expression of E-cadherin but decreased the expression of N-cadherin, vimentin, and snail-1. Besides, lower-level Cx43 is expressed in GC tissues compared with adjacent normal tissues. Additionally, dioscin downregulated the levels of p-Akt, p-mTOR, and p-PI3K. This research indicated that dioscin may inhibit EMT via increasing the expression of Cx43 and suppress the phosphorylation of PI3K/Akt signaling pathway and then inhibit the proliferation, invasion, and metastasis of GC.

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Impact of benzo[a]pyrene with other pollutants induce the molecular alternation in the biological system: Existence, detection, and remediation methods

Saravanakumar

SivaSantosh

Sathiyaseelan

et al. 2022

Environmental Pollution

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Cellular signaling crosstalk between Wnt signaling and gap junctions inbenzo[a]pyrene toxicity

Cited by 5 publications

References 58 publications

MgIG Attenuates Oxaliplatin-induced Hepatotoxicity through Suppression of Connexin 43 in Hepatic Stellate Cells

MgIG Attenuates Oxaliplatin-induced Hepatotoxicity through Suppression of Connexin 43 in Hepatic Stellate Cells

Retracted: Connexin 43 upregulation by dioscin‐inhibited gastric cancer metastasis by suppressing PI3K/Akt pathway

Impact of benzo[a]pyrene with other pollutants induce the molecular alternation in the biological system: Existence, detection, and remediation methods

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