title: Effects of tetrahydrocurcumin on hypoxia-inducible factor-1α and vascular endothelial growth factor expression in cervical cancer cell-induced angiogenesis in nude mice.
abstract: Tetrahydrocurcumin (THC), one of the important in vivo metabolites of curcumin, inhibits tumor angiogenesis. Its effects on angiogenesis in cervical cancer- (CaSki-) implanted nude mice and its mechanisms on hypoxia-inducible factor-1α and vascular endothelial growth factor expression were investigated. Female BALB/c nude mice were divided into control (CON) and CaSki-implanted groups (CaSki group). One month after the injection with cervical cancer cells, mice were orally administered vehicle or 100, 300, and 500 mg/kg of THC daily for 30 consecutive days. The microvascular density (MVD) was evaluated using the CD31 expression. VEGF, VEGFR-2, and HIF-1α expression were also detected by immunohistochemistry. The MVD in CaSki + vehicle group was significantly increased compared to the CON + vehicle group. Interestingly, when treated with THC at all doses, the CaSki group showed a significant smaller number of the MVD. The CaSki + vehicle group also showed significantly increased VEGF, VEGFR-2, and HIF-1α expressions, but they were downregulated when mice were treated with THC at all doses. THC demonstrated an inhibitory effect against tumor angiogenesis in CaSki-implanted nude mice model. This effect is likely to be mediated by the downregulation of HIF-1-α, VEGF expression, and its receptor. THC could be developed into a promising agent for cancer therapy in the future.
authors: Division of Physiology, Faculty of Medicine, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand.
authors: Bhornprom
authors: B
authors: Yoysungnoen
authors: Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Parvapan
authors: 0000-0002-9750-9609
authors: P
authors: Bhattarakosol
authors: Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
authors: Suthiluk
authors: S
authors: Patumraj
authors: Division of Physical Science, Faculty of Science and Technology, Huachiew Chalermprakiet University, Samut Prakan 10540, Thailand.
authors: Chatchawan
authors: C
authors: Changtam
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C096277:tetrahydrocurcumin; D040301:Vascular Endothelial Growth Factor Receptor-2; D003474:Curcumin