Licochalcone C induces cell cycle G1 arrest and apoptosis in human esophageal squamous carcinoma cells by activation of the ROS/MAPK signaling pathway.

Abstract

Along with changes in dietary habits and lifestyle, the incidence of esophageal cancer is increasing around the world. Since chemotherapy for esophageal cancer has significant side effects, phytochemicals have attracted attention as an alternative medicine. Licochalcone C (LCC) is a flavonoid compound extracted from Licorice, with a variety of clinical uses including anti-cancer, anti-inflammatory and anti-oxidant effects. Treatment with LCC for 48 h significantly decreased cell viability of esophageal squamous cell carcinoma (ESCC) cells in a dose- and time-dependent manner with IC50 values of 28 µM (KYSE 30), 36 µM (KYSE 70), 19 µM (KYSE 410), 28 µM (KYSE 450) and 26 µM (KYSE 510). LCC induced G1 arrest accompanied by decreased cyclin D1 expression and an increase in the levels of p21 and p27. LCC increased the levels of intracellular ROS, cytochrome C release, and multi-caspase activity, and decreased mitochondrial membrane potential. LCC induced the protein expression of ER stress markers (GRP78 and CHOP) and phosphorylation JNK, c-Jun and p38. We investigated the expression of pro-apoptotic and anti-apoptotic proteins to elucidate the mechanism of apoptosis. Our findings contribute to the understanding of apoptosis mechanism underlying LCC in ESCC cells and provide new insights into the potential clinical opportunities of LCC for ESCC treatment.

• Authors: Ah-Won Kwak, Joon-Seok Choi, Kangdong Liu, Mee-Hyun Lee, Young-Joo Jeon, Seung-Sik Cho, Goo Yoon, Ha-Na Oh, Jung-Il Chae, Jung-Hyun Shim
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 32 Issue 3 Pg. 132-143 (May 2020) ISSN: 1973-9478 [Electronic] England
• PMID: 32009586 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Chalcones
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Reactive Oxygen Species
• Cytochromes c
• Caspases
• licochalcone C

Topics

• Antineoplastic Agents (administration & dosage, pharmacology)
• Apoptosis (drug effects)
• Caspases (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chalcones (administration & dosage, pharmacology)
• Cytochromes c (biosynthesis)
• Dose-Response Relationship, Drug
• Endoplasmic Reticulum Chaperone BiP
• Esophageal Squamous Cell Carcinoma (drug therapy)
• G1 Phase (drug effects)
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Reactive Oxygen Species
• Time Factors