Licochalcone H Synthesized by Modifying Structure of Licochalcone C Extracted from Glycyrrhiza inflata Induces Apoptosis of Esophageal Squamous Cell Carcinoma Cells.

ABSTRACT

Esophageal cancer is one of the malignant cancers with a low 5-year survival rate. Licochalcone (LC) H, a chemically synthesized substance, is a regioisomer of LCC extracted from licorice. The purpose of this study was to determine whether LCH might have anticancer effect on human esophageal squamous cell carcinoma (ESCC) cell lines via apoptosis signaling pathway. After 48 h of treatment, IC50 of LCH in KYSE 30, KYSE 70, KYSE 410, KYSE 450, and KYSE 510 cells were 15, 14, 18, 15, and 16 µM, respectively. This study demonstrated that LCH potently suppressed proliferation of ESCC cells in a concentration- and time-dependent manner. LCH triggered G2/M-phase arrest by modulating expression levels of cdc2, cyclin B1, p21, and p27. LCH also induced apoptosis of ESCC cells through reactive oxygen species-mediated endoplasmic reticulum (ER) stress via JNK/p38 activation pathways. The anticancer effect of LCH was associated with ER stress and mitochondrial dysfunction. It also affected protein levels of Mcl-1, tBid, Bax, Bcl-2, cytochrome c, Apaf-1, PARP, cleaved-PARP, and ER stress-related proteins (GRP78 and CHOP). Our findings provide the first demonstration that LCH has anticancer effect on ESCC. Thus, LCH might have potential for preventing and/or treating human ESCC.