• Oncol Lett · Mar 2013

    Inhibition of cancer cell proliferation by midazolam by targeting transient receptor potential melastatin 7.

    • Yunling Dou, Yuan Li, Jingkao Chen, Sihan Wu, Xiao Xiao, Shanshan Xie, Lipeng Tang, Min Yan, Youqiong Wang, Jun Lin, Wenbo Zhu, and Guangmei Yan.
    • Department of Pharmacology, Zhongshan School of Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, P.R. China ; Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, P.R. China ;
    • Oncol Lett. 2013 Mar 1; 5 (3): 1010-1016.

    AbstractTransient receptor potential melastatin 7 (TRPM7), a Ca(2+)-permeable channel, has been demonstrated to be present in cancer cells and involved in their growth and proliferation. The present study used midazolam, a benzodiazepine class anesthesic, to pharmacologically intervene in the expression of TRPM7 and to inhibit cancer cell proliferation. Midazolam significantly inhibited the growth and proliferation of FaDu human hypopharyngeal squamous cell carcinoma cells, concurring with the induction of G(0)/G(1) cell cycle arrest and blockage of Rb activation. Central-type and peripheral-type benzodiazepine receptor antagonists did not abrogate proliferation inhibition by midazolam, while the specific TRPM7 agonist bradykinin reversed this effect. In addition, other benzodiazepines, diazepam and clonazepam also exhibited anti-proliferative activities. The inhibitory activity on cancer cell growth and proliferation, combined with the TRPM-dependent mechanism, reveals the anticancer potential of midazolam as a TRPM7 inhibitor and supports the suggestion that TRPM7 is a valuable target for pharmaceutical intervention.

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