HS-1793, a resveratrol analogue, downregulates the expression of hypoxia-induced HIF-1 and VEGF and inhibits tumor growth of human breast cancer cells in a nude mouse xenograft model
| Autor: | Bokyung Sung, Dong Hwan Kim, Jin-Ah Kim, Eunok Im, Hae Young Chung, Yung Hyun Choi, Yong Jung Kang, Hongsuk Suh, Nam Deuk Kim, Na-Lam Hwang, Seong Yeon Hwang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Vascular Endothelial Growth Factor A Cancer Research Angiogenesis Triple Negative Breast Neoplasms Naphthols Biology Resveratrol 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Nude mouse Breast cancer In vivo medicine Animals Humans Cell Proliferation Oncogene Resorcinols biology.organism_classification medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology Xenograft Model Antitumor Assays Vascular endothelial growth factor Gene Expression Regulation Neoplastic 030104 developmental biology Oncology chemistry 030220 oncology & carcinogenesis Cancer cell Cancer research MCF-7 Cells Female |
| Zdroj: | International journal of oncology. 51(2) |
| ISSN: | 1791-2423 |
| Popis: | A synthetic analogue of resveratrol, 4-(6-hydroxy-2-naphtyl)-1,3-benzenediol (HS-1793), with improved photosensitivity and stability profiles, has been recently reported to exert anticancer activity on various cancer cells. However, the molecular mechanism of action and in vivo efficacy of HS-1793 in breast cancer cells have not been fully investigated. In the present study, we evaluated the effect of HS-1793 on hypoxia-inducible factor-1α (HIF-1α), which drives angiogenesis and the growth of solid tumors, in addition to the in vivo therapeutic effects of HS-1793 on breast cancer cells. HS-1793 was found to inhibit hypoxia (1.0% oxygen)-induced HIF-1α expression at the protein level, and its inhibitory effect was more potent than that of resveratrol in MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, HS-1793 reduced the secretion and mRNA expression of vascular endothelial growth factor (VEGF), a key mediator of HIF-1-driven angiogenesis, without affecting cell viability. To evaluate the anticancer effects of HS-1793 in vivo, triple-negative MDA-MB-231 breast cancer xenografts were established in nude mice. HS-1793 significantly suppressed the growth of breast cancer tumor xenografts, without any apparent toxicity. Additionally, decreases in Ki-67, a proliferation index marker, and CD31, a biomarker of microvessel density, were observed in the tumor tissue. Expression of HIF-1 and VEGF was also downregulated in xenograft tumors treated with HS-1793. These in vivo results reinforce the improved anticancer activity of HS-1793 when compared with that of resveratrol. Overall, the present study suggests that the synthetic resveratrol analogue HS-1793 is a potent antitumor agent that inhibits tumor growth via the regulation of HIF-1, and demonstrates significant therapeutic potential for solid cancers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|