α-Solanine inhibits vascular endothelial growth factor expression by down-regulating the ERK1/2-HIF-1α and STAT3 signaling pathways.

Abstract

In tumors, vascular endothelial growth factor (VEGF) contributes to angiogenesis, vascular permeability, and tumorigenesis. In our previous study, we found that α-solanine, which is widespread in solanaceae, has a strong anti-cancer effect under normoxia. However, it is unknown whether α-solanine has a similar effect under hypoxia. We used cobalt chloride (CoCl2) to mimic hypoxia in vitro. HIF-1α, which is almost undetectable under normoxia, was significantly increased. Simultaneously, another regulator of VEGF, STAT3, was also significantly activated by CoCl2. We utilized α-solanine in co-culture with CoCl2. α-solanine decreased the expression of VEGF and loss of E-cadherin. α-solanine also suppressed the activation of phospho-ERK1/2 (p-ERK1/2), HIF-1α, and STAT3 signaling. The results provide new evidence that α-solanine has a strong anti-cancer effect via the ERK1/2-HIF-1α and STAT3 signaling pathways and suggest that it may be a potential new drug.

• Authors: Zhengde Wen, Chaohao Huang, Yaya Xu, Yuwu Xiao, Lili Tang, Juji Dai, Hongwei Sun, Bicheng Chen, Mengtao Zhou
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 771 Pg. 93-8 (Jan 15 2016) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 26688571 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Cadherins
• Hypoxia-Inducible Factor 1
• STAT3 Transcription Factor
• STAT3 protein, human
• Vascular Endothelial Growth Factor A
• alpha-solanine
• Solanine
• Cobalt
• cobaltous chloride

Topics

• Cadherins (biosynthesis, genetics)
• Cell Line, Tumor
• Cobalt (pharmacology)
• Coculture Techniques
• Down-Regulation
• Humans
• Hypoxia-Inducible Factor 1 (biosynthesis, genetics)
• MAP Kinase Signaling System (drug effects)
• Pancreatic Neoplasms (drug therapy, genetics)
• STAT3 Transcription Factor (drug effects)
• Signal Transduction (drug effects)
• Solanine (pharmacology)
• Vascular Endothelial Growth Factor A (antagonists & inhibitors, biosynthesis)