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

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 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.

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 Ca 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.