Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells

Gap junctions and the propagation of cell survival and cell death signals

“…113 Alternatively, the down regulation of Bcl-2 may result from signal transduction through secondary, down stream elements since Cx43 exhibits SH2 and SH3 as well as ZO1 binding sites. 111,[114][115][116] Another channel-independent function of Cxs is related to resistance to injury. Recently, it was shown that the forced expression of Cx43 as well as two other members of the Cx family (Cx32 and Cx40) protects cultured glial cells against cell injury.…”

“…In addition Qin et al 110 demonstrated in human breast tumor cells that Cx43 and Cx26 induce their tumor-suppressing properties by a mechanism that is independent of significant gap junction channels inhibition. Huang et al 111 showed that induction of apoptosis by the tumor-suppressor gene, Cx43 in human glioblastoma cells in response to chemotherapeutic drugs is mediated by down regulation of the apoptosis inhibitor protein Bcl-2 and may be due to Cx43 action that is not directly related to gap junctional channel formation. The mechanism for the regulation of Bcl-2 expression by Cx43 is currently unknown.…”

“…This proposed scheme is summarized from the following references. [45][46][47][50][51][52][53][54]56,57,[70][71][72][73][74]76,85,86,98,[100][101][102][103][104][105]111 carcinoma cell line that reduction of gap junction permeability with oleamide, did not affect the passage of Ca 2+ ions and did not abrogate coordinated cell death by clusters. This does however not mean that oleamide selectively restricts gap junction permeability to Ca 2+ ; it rather means that pathways other than gap junctions, e.g.…”

Protective Effect of the Natural Product, Chaetoglobosin K, on Lindane- and Dieldrin-induced Changes in Astroglia: Identification of Activated Signaling Pathways

“…However, while ChK appears to activate c-Raf, it has been reported to induce apoptosis in ras-transformed fibroblasts (4) and ras-transformed epithelial cells (unpublished observations). In addition, gap junctionmediated cell-cell communication and/or connexins have been correlated with increased apoptosis (39)(40)(41). In light of the observation that ChK stabilizes/restores gap junctionmediated cell-cell communication in the presence of tumor promoting compounds, it remains to be determined whether treatment of RG-2 astroglial cells with ChK for varying lengths of time is anti-apoptotic due to c-Raf activation or pro-apoptotic due to its effects on gap junction-mediated communication and, possibly, signaling pathways that are affected in ras-transformed cells.…”

Expression of gap junctional protein connexin43 during 4-nitroquinoline-1-oxide-induced rat tongue carcinogenesis

“…Connexin43 (Cx43) is the most widespread and key protein among multigene family of connexins. Researches found that Cx43 expressed in many kinds of normal tissues, such as skin, esophagus, cervix, prostate, lung, central nervous system and so on (Trosko and Ruch 1998;Huang et al 2001;Haass et al 2004). Their corresponding tumors were often associated with reduced expression or aberrant location of Cx43 protein, even loss of Cx43 expression.…”