Chapter 5 │ Page 184 reducing the expression of Cx43 proteins with siRNA in cultured astrocytes sensitized these resistant cells to H2O2-mediated apoptosis, indicating that Cx43 proteins have an anti-apoptotic e ect in normal astrocytes [151]. Thus, monoclonal antibody inhibitors of Cx43 proteins-composed connexon opening can be combined with oxidative stress-based cancer treatment, to improve cancer cell death. Therefore, the use of connexon blockers such as antibodies are also a promising therapeutic strategy during oxidative stress. However, further studies suggested that the use of antibodies should be treated carefully, as depending on the model, they may be considered anti- or pro-metastatic agents [154-156]. Considering the ability of GJs to enhance the intracellular accumulation of RONS, Wu et al. demonstrated that after PDT, the level of intracellular RONS was higher in HeLa cells with Cx32-GJs compared to those without. Hence, Cx32-GJs increased the e icacy of the treatment and this highlights the potential of GJs to transfer RONS to the cell interior [30] (Figure 5.1). The same research group also observed that when Cx26 proteins were not expressed or if the Cx26-GJs were blocked, the phototoxicity of Photofrin-mediated PDT in high-density cultures substantially reduced, emphasizing the importance of Cx26-GJs [157]. The GJs-mediated increase in PDT phototoxicity was associated with oxidative stress by RONS, Ca2+ ions, and lipid peroxide [157]. GJs have been shown to propagate localized oxidative insults in endothelial cells, while stimulating de-novo generation of RONS in bystander cells [38]. Interestingly, the oxidative insult propagated through GJs for many hours, over hundreds of microns from the primary photogeneration site [38]. These results highlight an impressive property of GJs to propagate oxidative stress-induced cell death. Cell exposure to ionizing radiation may a ect mitochondrial and membrane oxidases, leading to oxidative stress. Thus, Autsavapromporn et al. studied the involvement of oxidative stress and GJs in enhancing toxicity in α-particle-irradiated human fibroblast cells, and found that GJs were also able to propagate to
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