title: Inhibition of cancer cell proliferation by midazolam by targeting transient receptor potential melastatin 7.
abstract: Transient 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.
authors: 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 ;
authors: Yunling
authors: Y
authors: Dou
authors: Yuan
authors: Y
authors: Li
authors: Jingkao
authors: J
authors: Chen
authors: Sihan
authors: S
authors: Wu
authors: Xiao
authors: X
authors: Xiao
authors: Shanshan
authors: S
authors: Xie
authors: Lipeng
authors: L
authors: Tang
authors: Min
authors: M
authors: Yan
authors: Youqiong
authors: Y
authors: Wang
authors: Jun
authors: J
authors: Lin
authors: Wenbo
authors: W
authors: Zhu
authors: Guangmei
authors: G
authors: Yan
keywords: cell cycle arrest; human head and neck carcinoma; midazolam; proliferation; transient receptor potential melastatin 7