Wang Lin, Li Qing, Leung Lai Kwok, Wong Wing Tak
School of Life Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Cancer Med. 2025 Mar;14(5):e70705. doi: 10.1002/cam4.70705.
Colorectal cancer (CRC) is the third most common malignant tumor, and the fifth cause of cancer-related death in China, while chemotherapy is the primary strategy for CRC. Transient receptor potential (TRP) channels are non-selective cation channels while modulating the expression or activity of TRP channels results in the regulation of Ca influx. Previous studies have shown that TRP members with altered expression or channel activity are presented in CRC cells, which made them become promising therapeutic targets. Isoliquiritigenin (ISL), one of the major bioactive ingredients from traditional Chinese medicine licorice, was reported to exhibit anti-cancer properties such as induce apoptosis in CRC cells, but the underlying mechanism was not fully understood, whether its anticancer activity was related to regulating intracellular calcium and TRP channels remains for further investigation.
The study aims to investigate the effect of ISL on altering cytosol calcium in CRC cells and elucidate its potential molecular mechanism.
The study was conducted on 2 CRC cell lines HT29 and HCT116. Changes of cytosol calcium was indicated by live cell Ca imaging. Expression level of TRPV1 was determined by western blot. Cell apoptosis was detected by flow cytometry with Annexin V-FITC/PI staining.
ISL significantly increased cytosol calcium in HT29 and HCT116 cells. The ISL-induced increasing calcium ions were from both calcium influx and intracellular calcium release. ISL co-culture directly upregulated the expression of transient receptor potential vanilloid-1 (TRPV1) in colon cancer cells. Inhibition of TRPV1 by capsazepine (CapZ) abrogated the ISL-induced calcium influx and ISL-induced apoptosis in HT29 and HCT116 cells.
This study illustrates, for the first time, that ISL increased cytosol calcium concentration and induced apoptosis via TRPV1 in colon cancer cells, giving a new understanding of the underlying mechanism of its anti-cancer ability and making it a potential regulator for TRPV1.
结直肠癌（CRC）是中国第三大常见恶性肿瘤，也是癌症相关死亡的第五大原因，而化疗是CRC的主要治疗策略。瞬时受体电位（TRP）通道是一种非选择性阳离子通道，调节TRP通道的表达或活性会导致Ca内流的调节。先前的研究表明，CRC细胞中存在表达或通道活性改变的TRP成员，这使其成为有前景的治疗靶点。异甘草素（ISL）是中药甘草的主要生物活性成分之一，据报道具有抗癌特性，如诱导CRC细胞凋亡，但其潜在机制尚未完全阐明，其抗癌活性是否与调节细胞内钙和TRP通道有关仍有待进一步研究。
本研究旨在探讨ISL对CRC细胞胞浆钙的影响，并阐明其潜在的分子机制。
本研究以2种CRC细胞系HT29和HCT116为研究对象。通过活细胞Ca成像检测胞浆钙的变化。采用蛋白质免疫印迹法检测TRPV1的表达水平。采用Annexin V-FITC/PI染色，通过流式细胞术检测细胞凋亡。
ISL显著增加HT29和HCT116细胞的胞浆钙。ISL诱导的钙离子增加来自钙内流和细胞内钙释放。ISL共培养直接上调结肠癌细胞中瞬时受体电位香草酸受体1（TRPV1）的表达。辣椒素（CapZ）抑制TRPV1可消除ISL诱导的HT29和HCT116细胞钙内流和ISL诱导的细胞凋亡。
本研究首次表明，ISL通过TRPV1增加结肠癌细胞的胞浆钙浓度并诱导凋亡，为其抗癌能力的潜在机制提供了新的认识，并使其成为TRPV1的潜在调节剂。
