CaV channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics

被引:51
作者
Buchanan, Paul J. [1 ,2 ]
McCloskey, Karen D. [1 ]
机构
[1] Queens Univ Belfast, Sch Med Dent & Biomed Sci, Ctr Canc Res & Cell Biol, 97 Lisburn Rd, Belfast BT9 7AE, Antrim, North Ireland
[2] Dublin City Univ, Sch Nursing & Human Sci, Natl Inst Cellular Biotechnol, Dublin 9, Ireland
来源
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS | 2016年 / 45卷 / 07期
基金
英国医学研究理事会;
关键词
Cancer; Calcium channels; Repurposed drugs; ANTIHYPERTENSIVE MEDICATION USE; ALPHA(1C) CA(V)1.2 SUBUNIT; VOLTAGE-DEPENDENT CALCIUM; CHROMOGRANIN-A SECRETION; T-TYPE; PROSTATE-CANCER; BREAST-CANCER; CELL-PROLIFERATION; OVARIAN-CANCER; INTRACELLULAR CALCIUM;
D O I
10.1007/s00249-016-1144-z
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (Ca-V) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the Ca-V channel family are classified according to expression of their poreforming alpha-subunit; moreover, co-expression of accessory alpha 2 delta, beta and gamma confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics. Ca-V channels have traditionally been studied in excitable cells including neurones, smooth muscle, skeletal muscle and cardiac cells, and drugs targeting the channels are used in the treatment of hypertension and epilepsy. There is emerging evidence that several Ca-V channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of Ca-V channels also have non-canonical functions and are involved in transcriptional regulation of the expression of other proteins including potassium channels. Pharmacological studies show that Ca-V canonical function contributes to the fundamental biology of proliferation, cell-cycle progression and apoptosis. This raises the intriguing possibility that calcium channel blockers, approved for the treatment of other conditions, could be repurposed to treat particular cancers. Further research will reveal the full extent of both the canonical and non-canonical functions of Ca-V channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.
引用
收藏
页码:621 / 633
页数:13
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