Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1α expression during tumor progression.

Abstract

During tumor progression, hypoxia-inducible factor 1 (HIF-1) plays a critical role in tumor angiogenesis and tumor growth by regulating the transcription of several genes in response to a hypoxic environment and changes in growth factors. This study was designed to investigate the effects of cinnamic aldehyde (CA) on tumor growth and angiogenesis and the mechanisms underlying CA's anti-angiogenic activities. We found that CA administration inhibits tumor growth and blocks tumor angiogenesis in BALB/c mice. In addition, CA treatment decreased HIF-1α protein expression and vascular endothelial growth factor (VEGF) expression in mouse tumors and Renca cells exposed to hypoxia in vitro. Interestingly, CA treatment did not affect the stability of von Hippel-Lindau protein (pVHL)-associated HIF-1α and CA attenuated the activation of mammalian target of rapamycin (mTOR) pathway. Collectively, these findings strongly indicate that the anti-angiogenic activity of CA is, at least in part, regulated by the mTOR pathway-mediated suppression of HIF-1α protein expression and these findings suggest that CA may be a potential drug for human cancer therapy.

• Authors: Woom-Yee Bae, Jae-Sun Choi, Ja-Eun Kim, Joo-Won Jeong
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 98 Issue 1 Pg. 41-50 (Nov 01 2015) ISSN: 1873-2968 [Electronic] England
• PMID: 26297910 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• Acrolein
• mTOR protein, mouse
• TOR Serine-Threonine Kinases
• cinnamaldehyde

Topics

• Acrolein (analogs & derivatives, pharmacology)
• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Cell Line, Tumor
• Cell Movement
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hypoxia (complications, metabolism)
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, genetics, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Neoplasms, Experimental (blood supply, drug therapy)
• Neovascularization, Pathologic (prevention & control)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• TOR Serine-Threonine Kinases (genetics, metabolism)