Propofol inhibits gap junctions by attenuating sevoflurane-induced cytotoxicity against rat liver cells in vitro

Huang, Fei; Li, Shangrong; Gan, Xiaoliang; Ren, Weirong; Chen, Zhonggang

doi:10.1097/01.eja.0000435059.98170.da

Cited by 10 publications

(7 citation statements)

References 29 publications

(22 reference statements)

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“…GJIC-dependent effects of Cxs, including Cx32, Cx43 and Cx26, on the sensitivity of antineoplastics have been reported in many studies 22 , 52 , 53 . In the present study, we observed that 18α-GA, a well-defined GJIC inhibitor, restored the inhibitory role of Cx43 in TGF-β1-induced EMT and TAM insensitivity in TAM-sensitive cells (Fig.…”

Section: Discussionmentioning

confidence: 89%

Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway

Wu¹,

Zhou²,

Hou³

et al. 2021

Int. J. Biol. Sci.

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Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.

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Section: Discussionmentioning

confidence: 89%

Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway

Wu¹,

Zhou²,

Hou³

et al. 2021

Int. J. Biol. Sci.

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“…To determine whether GJIC was required for the increase of adriamycin-induced cytotoxicity in cells with GJIC, the breast cancer cells Hs578T and MCF-7 were treated with chemical modulators of GJs prior and during exposure to 6 µM adriamycin [inhibitor, oleamide (22,23) or 18-α-GA (24,25); potentiator, RA (21,26)] at high density (GJ formed) or low density (no GJ formed). Fig.…”

Section: Influence Of Gj Potentiator On the Cytotoxicity Of Adriamycinmentioning

confidence: 99%

Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

Jiang

Dong

et al. 2016

Oncology Letters

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Abstract. Gap junctions (GJs) serve the principal role in the antineoplastic (cytotoxicity and induced apoptosis) effect of chemical drugs. The aim of the present study was to determine the effect of GJ intercellular communication (GJIC) composed of connexin 43 (Cx43) on adriamycin cytotoxicity in breast cancer cells. Four cell lines (Hs578T, MCF-7, MDA-MB-231 and SK-BR-3) with different degree of malignancy were used in the study. The results of western blotting and immunofluorescence revealed that, in Hs578T and MCF-7 cells, which have a low degree of malignancy, the expression levels of Cx43 and GJIC were higher than those in MDA-MB-231 and SK-BR-3 cells (which have a high degree of malignancy). In Hs578T and MCF-7 cells, where GJ could be formed, the function of GJ was modulated by a pharmacological potentiators [retinoid acid (RA)]/inhibitors [oleamide and 18-α-glycyrrhetinic acid (18-α-GA)] and small interfering RNA (siRNA). In high-density cells (where GJ was formed), enhancement of GJ function by RA increased the cytotoxicity of adriamycin, while inhibition of GJ function by oleamide/18-α-GA and siRNA decreased the cytotoxicity caused by adriamycin. Notably, the modulation of GJ did not affect the survival of cells treated with adriamycin when cells were in low density (no GJ was formed). The present study illustrated the association between GJIC and the antitumor effect of adriamycin in breast cancer cells. The cytotoxicity of adriamycin on breast cancer cells was increased when the function of gap junctions was enhanced.

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“…It has been reported that propofol mediates protective effects against cisplatin-induced injury, including the upregulation of endothelial adhesion molecules in human umbilical vein endothelial cells (13) and the attenuation of toxic oxidative stress (14). In addition, propofol has been shown to suppress GJIC composed of Cx32 in various cell lines (15,16). Our previous studies demonstrated that tramadol and flurbiprofen, two commonly used analgesics, depressed the cytotoxicity of cisplatin via inhibiting GJIC (17).…”

Section: Introductionmentioning

confidence: 97%

Propofol depresses cisplatin cytotoxicity via the inhibition of gap junctions

Zhang

Wang

et al. 2016

Molecular Medicine Reports

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The general anesthetic, propofol, affects chemotherapeutic activity, however, the mechanism underlying its effects remains to be fully elucidated. Our previous study showed that tramadol and flurbiprofen depressed the cytotoxicity of cisplatin via the inhibition of gap junction (GJ) intercellular communication (GJIC) in connexin (Cx)32 HeLa cells. The present study investigated whether the effects of propofol on the cytotoxicity of cisplatin were mediated by GJ in U87 glioma cells and Cx26‑transfected HeLa cells. Standard colony formation assay was used to determine the cytotoxicity of cisplatin. Parachute dye coupling assay was used to measure GJ function, and western blot analysis was used to determine the expression levels of Cx32. The results revealed that exposure of the U87 glioma cells and the Cx26-transfected HeLa cells to cisplatin for 1 h reduced clonogenic survival in low density cultures (without GJs) and high density cultures (with GJs). However, the toxic effect was higher in the high density culture. In addition, pretreatment of the cells with propofol significantly reduced cisplatin‑induced cytotoxicity, but only in the presence of functional GJs. Furthermore, propofol significantly inhibited dye coupling through junctional channels, and a long duration of exposure of the cells to propofol downregulated the expression levels of Cx43 and Cx26. These results demonstrated that the inhibition of GJIC by propofol affected the therapeutic efficacy of chemotherapeutic drugs. The present study provides evidence of a novel mechanism underlying the effects of analgesics in counteracting chemotherapeutic efficiency.

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Propofol inhibits gap junctions by attenuating sevoflurane-induced cytotoxicity against rat liver cells in vitro

Abstract: This study provides the first direct evidence that sevoflurane-induced cytotoxicity, which is mediated through gap junctions, is attenuated by propofol, possibly by its action on Cx32 homomeric or heteromeric complexes.

Cited by 10 publications

References 29 publications

Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway

Cx43 deficiency confers EMT-mediated tamoxifen resistance to breast cancer via c-Src/PI3K/Akt pathway

Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

Propofol depresses cisplatin cytotoxicity via the inhibition of gap junctions

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