Methylselenocysteine Promotes Etoposide Cytotoxicity by Enhancing Homotypic Gap Junctions Composed of Connexin 26].

Zhen-Yu Lyu, Wen-Bin Ji, Qian-Qian Cheng, Xue-Li Zhou, Wei Wang, Yan Yang

Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 2023 May

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To investigate the effect of methylselenocysteine (MSC) on the function of homotypic gap junction (GJ) composed of connexin (Cx) 26 and its regulation of chemotherapeutic drug cytotoxicity. The Tet-on HeLa cells transfected with and stably expressing Cx26 were used as the tool cells. Effects of MSC on cell growth, GJ function, and Cx26 protein expression were examined by MTT method, parachute assay, and Western blot analysis, respectively. The cytotoxicity of chemotherapeutic drugs was determined by standard colony-forming assay, and the relationship between MSC's effect on cytotoxicity of these chemotherapeutic drugs and its regulation of GJ was further analyzed. In Tet-on HeLa cells, doxycycline (Dox) can induce the expression of Cx26, which could then form functional GJs. Within a concentration range of 50 μmol/L, MSC had no significant effect on HeLa cell growth. Non-toxic concentrations of MSC can enhance GJs in a concentration-dependent manner and exert its effect at the nanomolar level. This effect was associated with an induction of Cx26 protein expression by MSC. Among the three common chemotherapeutic agents with different mechanisms of action, etoposide (Eto) presented cytotoxicity differences between HeLa cells cultured at low density (nonconfluent, no GJ formed) and high density (confluent, GJ formed). What's more, the inhibitory effect of Eto combined with MSC on HeLa cell colony formation was stronger than that of Eto alone, and this effect occurred only in HeLa cells with GJ formation. MSC can potentiate the cytotoxicity of Eto by enhancing the GJs composed of Cx26, indicating that combined strategy of selenide and chemotherapy shows potential value in the treatment of malignant tumors. Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).

Citation

Zhen-Yu Lyu, Wen-Bin Ji, Qian-Qian Cheng, Xue-Li Zhou, Wei Wang, Yan Yang. Methylselenocysteine Promotes Etoposide Cytotoxicity by Enhancing Homotypic Gap Junctions Composed of Connexin 26]. Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition. 2023 May;54(3):532-538