Chrysin inhibits cell invasion by inhibition of Recepteur d'origine Nantais via suppressing early growth response-1 and NF-κB transcription factor activities in gastric cancer cells.

Abstract

Cell invasion is one of crucial reasons for cancer metastasis and malignancy. Recepteur d'origine Nantais (RON) has been reported to play an important role in the cancer cell invasion process. High accumulation and activation of RON has been implicated in gastric adenocarcinoma AGS cells. Chrysin is a naturally occurring phytochemical, a type of flavonoid, which has been reported to suppress tumor metastasis. However, the effects of chrysin on RON expression in gastric cancer are not well studied. In the present study, we examined whether chrysin affects RON expression in gastric cancer, and if so, its underlying mechanism. We examined the effect of chrysin on RON expression and activity, via RT-PCR, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin significantly inhibited endogenous and inducible RON expression in a dose-dependent manner. After demonstrating that Egr-1 and NF-κB are the critically required transcription factors for RON expression, we discovered that chrysin suppressed Egr-1 and NF-κB transcription factor activities. Additionally, the phorbol-12-myristate-13-acetate- (PMA) induced cell invasion was partially abrogated by chrysin and an RON antibody. Our results suggest that chrysin has anticancer effects at least by suppressing RON expression through blocking Egr-1 and NF-κB in gastric cancer AGS cells.

• Authors: Yong Xia, Sen Lian, Pham Ngoc Khoi, Hyun Joong Yoon, Jae Young Han, Kee Oh Chay, Kyung Keun Kim, Young Do Jung
• Journal: International journal of oncology (Int J Oncol) Vol. 46 Issue 4 Pg. 1835-43 (Apr 2015) ISSN: 1791-2423 [Electronic] Greece
• PMID: 25625479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• EGR1 protein, human
• Early Growth Response Protein 1
• Flavonoids
• NF-kappa B
• chrysin
• RON protein
• Receptor Protein-Tyrosine Kinases

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Dose-Response Relationship, Drug
• Early Growth Response Protein 1 (genetics, metabolism)
• Flavonoids (pharmacology)
• Humans
• NF-kappa B (genetics, metabolism)
• Promoter Regions, Genetic (drug effects)
• Receptor Protein-Tyrosine Kinases (genetics, metabolism)
• Stomach Neoplasms (drug therapy, genetics, metabolism)