Isoliquiritigenin Suppressed Esophageal Squamous Carcinoma Growth by Blocking EGFR Activation and Inducing Cell Cycle Arrest

Isoliquiritigenin (ILQ) is a natural product isolated from licorice root which has served as traditional Chinese medicine for a long time. Recently, the antitumor effects of ILQ have been widely studied in various cancers, but the role and related mechanisms of ILQ in esophageal squamous carcinoma cells (ESCC) are still poorly understood. In our studies, ILQ showed profound antitumor activities in ESCC cells. In vitro, ILQ substantially inhibited cell proliferation and anchorage-independent growth in a panel of human ESCC cells. Mechanism studies showed that EGFR signaling pathway played an important role for ILQ to exert its antitumor activity in ESCC. Exposure to isoliquiritigenin substantially decreased EGF-induced EGFR activation and its downstream Akt and ERK1/2 signaling pathway. EGFR knockdown with shRNA in ESCC cell significantly reduced the sensitivity of cancer cells to ILQ. Moreover, it was found that ILQ had a significantly inhibitory effect on AP-1 family, the protein of Jun and Fos subfamilies was substantially downregulated, and the transcriptional activity of AP-1 family was dramatically suppressed by ILQ. By reducing the expression of cyclin D1, ESCC cells were induced G0/G1 arrest, and cell division was substantially blocked. Finally, the antitumor potency of ILQ was validated in xenograft models and the tumor growth was prominently restrained by ILQ. Briefly, our study showed that ILQ, or its analogue, appeared to be a promising new therapeutic agent for ESCC management.