title: 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: Department of Biomedical Science, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Woom-Yee
authors: WY
authors: Bae
authors: Department of Biomedical Science, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Jae-Sun
authors: JS
authors: Choi
authors: Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors: Ja-Eun
authors: JE
authors: Kim
authors: Department of Biomedical Science, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea; Department of Anatomy and Neurobiology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: jjeong@khu.ac.kr.
authors: Joo-Won
authors: JW
authors: Jeong
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000171:Acrolein; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; C012843:cinnamaldehyde
keywords: Angiogenesis; Cinnamic aldehyde; Cinnamic aldehyde (PubChem CID: 637511); Hypoxia-inducible factor-1α; MG132 (PubChem CID: 462382); Rapamycin (PubChem CID: 71296106); Tumor