Research Article Effects of Tetrahydrocurcumin on Hypoxia-Inducible Factor-1 and Vascular Endothelial Growth Factor Expression in Cervical Cancer Cell-Induced Angiogenesis in Nude Mice Bhornprom Yoysungnoen, 1 Parvapan Bhattarakosol, 2 Suthiluk Patumraj, 3 and Chatchawan Changtam 4 1 Division of Physiology, Faculty of Medicine, hammasat University, Rangsit Campus, Pathumthani 12120, hailand 2 Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, hailand 3 Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, hailand 4 Division of Physical Science, Faculty of Science and Technology, Huachiew Chalermprakiet University, Samut Prakan 10540, hailand Correspondence should be addressed to Bhornprom Yoysungnoen; pornprom y@hotmail.com Received 21 December 2014; Revised 24 January 2015; Accepted 26 January 2015 Academic Editor: Weibo Cai Copyright © 2015 Bhornprom Yoysungnoen et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tetrahydrocurcumin (THC), one of the important in vivo metabolites of curcumin, inhibits tumor angiogenesis. Its efects on angiogenesis in cervical cancer- (CaSki-) implanted nude mice and its mechanisms on hypoxia-inducible factor-1 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 ater 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. he microvascular density (MVD) was evaluated using the CD31 expression. VEGF, VEGFR-2, and HIF-1 expression were also detected by immunohistochemistry. he MVD in CaSki + vehicle group was signiicantly increased compared to the CON + vehicle group. Interestingly, when treated with THC at all doses, the CaSki group showed a signiicant smaller number of the MVD. he CaSki + vehicle group also showed signiicantly increased VEGF, VEGFR-2, and HIF-1 expressions, but they were downregulated when mice were treated with THC at all doses. THC demonstrated an inhibitory efect against tumor angiogenesis in CaSki-implanted nude mice model. his efect is likely to be mediated by the downregulation of HIF-1-, VEGF expression, and its receptor. THC could be developed into a promising agent for cancer therapy in the future. 1. Introduction Cervical tumors frequently have a high vascular density which is responsible for spontaneous bleeding, a common symptom of cervical cancer. here is an urgent need for the development of novel agents to combat this type of cancer. Antiangiogenic agents have been identiied as promising treatments that may enhance therapeutic outcomes when used in combination with chemotherapy. Currently, there are a number of biological agents in clinical development that inhibit tumor angiogenesis by targeting vascular endothelial growth factor (VEGF) and its signaling. VEGF, also known as vascular permeability factor (VPF), is a major mediator of tumor angiogenesis and is tightly controlled by oxygen tension [1]. Hypoxia induces the expres- sion of VEGF and its receptor via hypoxia inducible factor- 1 (HIF-1)[2]. VEGF promotes mobilization of endothelial progenitor cells, cell proliferation, migration, and survival [3]. VEGF can also induce the leakage of blood vessels which contributes to an increasing edema around the tumor tissue [4]. With the efect of VEGF, blood vessels become incapable of providaing eicient blood low, thus creating the hypoxic condition to the tumor [5] which in turn stimulates the continuous production of VEGF. his continuous cycle of Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 391748, 11 pages http://dx.doi.org/10.1155/2015/391748