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Biomed Res Int. 2015;2015:391748. doi: 10.1155/2015/391748. Epub 2015 Feb 18.

Effects of tetrahydrocurcumin on hypoxia-inducible factor-1α and vascular endothelial growth factor expression in cervical cancer cell-induced angiogenesis in nude mice.

Author information

1
Division of Physiology, Faculty of Medicine, Thammasat University, Rangsit Campus, Pathumthani 12120, Thailand.
2
Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
3
Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
4
Division of Physical Science, Faculty of Science and Technology, Huachiew Chalermprakiet University, Samut Prakan 10540, Thailand.

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.

PMID:
25789317
PMCID:
PMC4348612
DOI:
10.1155/2015/391748
[Indexed for MEDLINE]
Free PMC Article

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