Baicalein inhibits migration and invasion of gastric cancer cells through suppression of the TGF-β signaling pathway.

Abstract

The transforming growth factor-β (TGF-β) signaling pathway exhibits an important role in cancer invasion and metastasis. Excessive expression of TGF-β activates Smad4, leading to the upregulation of downstream metastasis-associated genes. Thus, the inhibition of the TGF-β/Smad4 signaling pathway may be a novel strategy for treatment of cancer metastasis. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to exert strong anti-tumor activity towards various types of cancer. In the present study the effect of baicalein on migration and invasion of cancer cells was evaluated using wound-healing and Transwell assays. In order to investigate the possible molecular mechanisms of the anti-metastatic effects of baicalein, quantitative polymerase chain reaction (qPCR) and western blot analyses were performed to examine the effect on the expression of TGF‑β, Smad4, N-cadherin, vimentin, ZEB1 and ZEB2. It was determined that baicalein inhibited the migration and invasion of AGS cells by suppressing the TGF-β/Smad4 signaling pathway. In addition, baicalein treatment reduced the expression of the metastasis-associated N-cadherin, vimentin, ZEB1 and ZEB2, downstream target genes of the TGF‑β/Smad4 signaling pathway. Collectively, these results suggest that inhibition of the metastasis of cancer cells via inactivation of TGF-β/Smad4 signaling is one of the mechanisms by which baicalein may treat cancer.

• Authors: Fenglin Chen, Mingkai Zhuang, Jun Peng, Xiaozhong Wang, Tingxuan Huang, Sanmei Li, Manqiang Lin, Hongming Lin, Yating Xu, Jianying Li, Zhixin Chen, Yuehong Huang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 10 Issue 4 Pg. 1999-2003 (Oct 2014) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25109410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Cadherins
• Flavanones
• Homeodomain Proteins
• Repressor Proteins
• Smad4 Protein
• Transcription Factors
• Transforming Growth Factor beta
• Vimentin
• ZEB1 protein, human
• ZEB2 protein, human
• Zinc Finger E-box Binding Homeobox 2
• Zinc Finger E-box-Binding Homeobox 1
• baicalein

Topics

• Antineoplastic Agents, Phytogenic (toxicity)
• Cadherins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Flavanones (toxicity)
• Homeodomain Proteins (genetics, metabolism)
• Humans
• Plant Roots (chemistry, metabolism)
• Repressor Proteins (genetics, metabolism)
• Scutellaria baicalensis (chemistry, metabolism)
• Signal Transduction (drug effects)
• Smad4 Protein (genetics, metabolism)
• Stomach Neoplasms (pathology)
• Transcription Factors (genetics, metabolism)
• Transforming Growth Factor beta (genetics, metabolism)
• Vimentin (genetics, metabolism)
• Zinc Finger E-box Binding Homeobox 2
• Zinc Finger E-box-Binding Homeobox 1