Licorice Extract Isoliquiritigenin Increased Cytosol Calcium and Induced Apoptosis in Colon Cancer Cells via Transient Receptor Potential Vanilloid-1

IF 3.1 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-02-27 DOI:10.1002/cam4.70705

Lin Wang, Qing Li, Lai Kwok Leung, Wing Tak Wong

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引用次数: 0

Abstract

Background

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 Ca²⁺ 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.

Objective

The study aims to investigate the effect of ISL on altering cytosol calcium in CRC cells and elucidate its potential molecular mechanism.

Methods

The study was conducted on 2 CRC cell lines HT29 and HCT116. Changes of cytosol calcium was indicated by live cell Ca²⁺ imaging. Expression level of TRPV1 was determined by western blot. Cell apoptosis was detected by flow cytometry with Annexin V-FITC/PI staining.

Results

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.

Conclusions

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.

Abstract Image

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甘草提取物异甘草素通过瞬时受体电位香草素-1增加结肠癌细胞胞浆钙并诱导细胞凋亡

结直肠癌（CRC）是中国第三大最常见的恶性肿瘤，也是癌症相关死亡的第五大原因，而化疗是结直肠癌的主要治疗策略。瞬时受体电位（TRP）通道是非选择性阳离子通道，而调节TRP通道的表达或活性可调节Ca2+内流。先前的研究表明，在CRC细胞中存在表达或通道活性改变的TRP成员，这使其成为有希望的治疗靶点。异甘草素（ISL）是中药甘草的主要生物活性成分之一，据报道其具有诱导结直肠癌细胞凋亡等抗癌特性，但其机制尚不完全清楚，其抗癌活性是否与调节细胞内钙和TRP通道有关，有待进一步研究。目的探讨ISL对结直肠癌细胞细胞质钙的影响，并阐明其可能的分子机制。方法对2种结直肠癌细胞系HT29和HCT116进行研究。活细胞Ca2+成像显示胞浆钙的变化。western blot检测TRPV1的表达水平。Annexin V-FITC/PI染色流式细胞术检测细胞凋亡情况。结果ISL可显著提高HT29和HCT116细胞的细胞质钙含量。isl诱导的钙离子增加来自钙内流和细胞内钙释放。ISL共培养可直接上调结肠癌细胞中瞬时受体电位香草素-1 （TRPV1）的表达。capsazepine （CapZ）对HT29和HCT116细胞TRPV1的抑制作用消除了isli诱导的钙内流和凋亡。结论本研究首次阐明ISL可通过结肠癌细胞TRPV1增加细胞质钙浓度，诱导细胞凋亡，对其抗癌作用机制有了新的认识，ISL可能是TRPV1的潜在调节因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.