Astemizole is a potent anti-histamine compound that antagonizes the histamine H1-receptor with an IC50 value of 4nM [1]. Astemizole can inhibit the KCa1.1 potassium ion channel in osteosarcoma cells, with an IC50 value of 0.135μM [2]. Astemizole has been widely used as an anti-cancer agent, inhibiting the growth of various tumor cells[3].
In vitro, Astemizole treatment for 6 days significantly inhibited cell death in BT-474 cells, with an IC50 value of 1.72μM[4]. 1µM of Astemizole was pre-treated for 12 hours, which significantly restored the viability of human umbilical vein endothelial cells (HUVECs) under oxidative stress and eliminated the intracellular reactive oxygen species (ROS) induced by H2O2[5]. Treatment with 5µM Astemizole for 96 hours can target the expression of Eag1 protein, induce apoptosis in HeLa cells, and inhibit cell proliferation[6].
In vivo, Astemizole treatment for 7 days (20mg/kg/day; p.o.) can effectively reverse the leakage of albumin across the blood-retinal barrier in experimental diabetes[7]. Oral administration of 50mg/kg of Astemizole daily for 12 weeks significantly inhibited the occurrence of hepatocellular carcinoma (HCC) in rats induced by diethylnitrosamine[8].
References:
[1] Laduron P M, Janssen P F, Gommeren W, et al. In vitro and in vivo binding characteristics of a new long-acting histamine H1 antagonist, astemizole[J]. Molecular Pharmacology, 1982, 21(2): 294-300.
[2] Mészáros B, Csoti A, Szanto T G, et al. The hEag1 K+ Channel Inhibitor Astemizole Stimulates Ca2+ Deposition in SaOS-2 and MG-63 Osteosarcoma Cultures[J]. International journal of molecular sciences, 2022, 23(18): 10533.
[3] Garcia-Quiroz J, Camacho J. Astemizole: an old anti-histamine as a new promising anti-cancer drug[J]. Anti-Cancer Agents in Medicinal Chemistry-Anti-Cancer Agents), 2011, 11(3): 307-314.
[4] García-Quiroz J, González-González M E, Díaz L, et al. Astemizole, an inhibitor of ether-à-go-go-1 potassium channel, increases the activity of the tyrosine kinase inhibitor gefitinib in breast cancer cells[J]. Revista de investigación clínica, 2019, 71(3): 186-194.
[5] Tian J N, Shi X D, Wang X K, et al. Astemizole protects against human umbilical vein endothelial cell injury induced by hydrogen peroxide via the p53 signaling pathway[J]. Molecular Medicine Reports, 2017, 15(6): 4286-4290.
[6] de Guadalupe Chávez-López M, Hernández-Gallegos E, Vázquez-Sánchez A Y, et al. Antiproliferative and proapoptotic effects of astemizole on cervical cancer cells[J]. International Journal of Gynecological Cancer, 2014, 24(5): 824-828.
[7] Hollis T M, Sill H W, Butler C, et al. Astemizole reduces blood-retinal barrier leakage in experimental diabetes[J]. Journal of diabetes and its complications, 1992, 6(4): 230-235.
[8] de Guadalupe Chavez-Lopez M, Pérez-Carreón J I, Zuñiga-García V, et al. Astemizole-based anticancer therapy for hepatocellular carcinoma (HCC), and Eag1 channels as potential early-stage markers of HCC[J]. Tumor Biology, 2015, 36(8): 6149-6158.
Astemizole是一种强效抗组胺化合物，可拮抗组胺H1受体，IC50值为4nM[1]。Astemizole能抑制骨肉瘤细胞中的KCa1.1钾离子通道，IC50值为0.135µM[2]。Astemizole已被广泛用作抗癌剂，抑制多种肿瘤细胞的生长[3]。
在体外，Astemizole处理6天显著抑制了BT-474细胞的死亡，IC50值为1.72µM[4]。预处理1µM的Astemizole 12小时，显著恢复了氧化应激下的人脐静脉内皮细胞（HUVECs）活力，并消除了由H2O2诱导的细胞内活性氧（ROS）[5]。使用5µM的Astemizole处理96小时，可靶向抑制Eag1蛋白的表达，诱导HeLa细胞凋亡，并抑制细胞增殖[6]。
在体内，口服给予20mg/kg/day剂量的Astemizole，持续7天，能有效逆转实验性糖尿病中白蛋白跨血-视网膜屏障的渗漏[7]。每日口服50mg/kg剂量的Astemizole，连续12周，显著抑制了diethylnitrosamine诱导的大鼠肝细胞癌（HCC）的发生[8]。