Mibefradil; a T-type calcium channel blocker as a potential anti-cancer agent.

Matheou, Chrysanthi; Chandler, Stephen; Crea, Francesco; Faria, Nuno; Powell, Jonathan; McDonald, Fraser; Rietdorf, Katja and Bootman, Martin D. (2016). Mibefradil; a T-type calcium channel blocker as a potential anti-cancer agent. In: 14th International Meeting of the European Calcium Society, 25-29 Sep 2016, Valladolid, Spain.


T-type calcium channels are known to be involved in critical physiological functions such as neuronal excitability and cardiac pacemaking. Additionally, their involvement has been suggested for the proliferation and/or differentiation of cancer cells. Indeed, overexpression of T-type calcium channels has been demonstrated for several cancer cell types, as well as other rapidly proliferating cells. A clinical trial is currently underway to establish whether T-type calcium channel blockers could potentially be used as therapeutic anti-cancer agents. This project examined putative cytotoxicity/cytostatic effects of the T-type calcium channel blocker mibefradil, and the L-type calcium channel blocker verapamil, on a number of rapidly proliferating cell lines: PC3 (prostate cancer), HSC3 (skin cancer), HeLa (cervical cancer) and HaCaT (human keratinocyte). Cell viability was assessed using MTT assays performed 24 h after drug addition. We found that mibefradil caused a concentration-dependent inhibition of proliferation in all four cell lines with different sensitivities: IC50 HaCaT 12.9 μM < HSC3 19.9 μM < PC3 21.3 μM < HeLa 37.7 μM. In contrast, verapamil only showed a very modest effect on the proliferation of HaCaT cells when applied at 200 μM, and had no significant effect on the other cell types at any concentration used. These results show that selectively targeting T-type calcium channels can inhibit cell proliferation. Future experiments need to show whether this is a cytotoxic or a cytostatic effect, whether it is selective to fast proliferating cell lines like cancer cells, and how inhibition of T-type calcium channels leads decreased cell proliferation.

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