Myricetin exerts anti-proliferative, anti-invasive, and pro-apoptotic effects on esophageal carcinoma EC9706 and KYSE30 cells via RSK2.

Abstract

Myricetin, a common dietary flavonoid, is widely distributed in fruits and vegetables and is used as a health food supplement based on its anti-tumor properties. However, the effect and mechanisms of myricetin in esophageal carcinoma are not fully understood. Here, we demonstrated the effect of myricetin on the proliferation, apoptosis, and invasion of the esophageal carcinoma cell lines EC9706 and KYSE30 and explored the underlying mechanism and target protein(s) of myricetin. CCK-8 assay, transwell invasion assay, wound-healing assay, cell cycle analysis, and apoptosis assay were used to evaluate the effects of myricetin on cell proliferation, invasion, and apoptosis. Nude mouse tumor xenograft model was built to understand the interaction between myricetin and NTD RSK2. Pull-down assay was used to verify molecular mechanism. Myricetin inhibited proliferation and invasion and induced apoptosis of EC9706 and KYSE30 cells. Moreover, myricetin was shown to bind RSK2 through the NH2-terminal kinase domain. Finally, myricetin inhibited EC9706 and KYSE30 cell proliferation through Mad1 and induced cell apoptosis via Bad. Myricetin inhibits the proliferation and invasion and induces apoptosis in EC9706 and KYSE30 cells via RSK2. Myricetin exerts anti-proliferative, anti-invasive, and pro-apoptotic effects on esophageal carcinoma EC9706 and KYSE30 cells via RSK2. Our results provide novel insight into myricetin as a potential agent for the prevention and treatment of esophageal carcinoma.

• Authors: Wenqiao Zang, Tao Wang, Yuanyuan Wang, Min Li, Xiaoyan Xuan, Yunyun Ma, Yuwen Du, Kangdong Liu, Ziming Dong, Guoqiang Zhao
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 35 Issue 12 Pg. 12583-92 (Dec 2014) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25192723 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cell Cycle Proteins
• Flavonoids
• MAD1L1 protein, human
• Nuclear Proteins
• bcl-Associated Death Protein
• myricetin
• Ribosomal Protein S6 Kinases, 90-kDa
• ribosomal protein S6 kinase, 90kDa, polypeptide 3

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Carcinoma (genetics, metabolism, pathology)
• Cell Cycle (drug effects)
• Cell Cycle Proteins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Esophageal Neoplasms (genetics, metabolism, pathology)
• Female
• Flavonoids (chemistry, pharmacology)
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Gene Expression
• Humans
• Models, Molecular
• Molecular Conformation
• Nuclear Proteins (genetics, metabolism)
• Protein Binding
• Protein Interaction Domains and Motifs
• Ribosomal Protein S6 Kinases, 90-kDa (chemistry, metabolism)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays
• bcl-Associated Death Protein (genetics, metabolism)