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

  • Authors:
    • Dong Hwan Kim
    • Bokyung Sung
    • Jin-Ah Kim
    • Yong Jung Kang
    • Seong Yeon Hwang
    • Na-Lam Hwang
    • Hongsuk Suh
    • Yung Hyun Choi
    • Eunok Im
    • Hae Young Chung
    • Nam Deuk Kim
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  • Published online on: June 27, 2017     https://doi.org/10.3892/ijo.2017.4058
  • Pages: 715-723
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Abstract

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.
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August-2017
Volume 51 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kim DH, Sung B, Kim J, Kang YJ, Hwang SY, Hwang N, Suh H, Choi YH, Im E, Chung HY, Chung HY, et al: 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. Int J Oncol 51: 715-723, 2017.
APA
Kim, D.H., Sung, B., Kim, J., Kang, Y.J., Hwang, S.Y., Hwang, N. ... Kim, N.D. (2017). 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. International Journal of Oncology, 51, 715-723. https://doi.org/10.3892/ijo.2017.4058
MLA
Kim, D. H., Sung, B., Kim, J., Kang, Y. J., Hwang, S. Y., Hwang, N., Suh, H., Choi, Y. H., Im, E., Chung, H. Y., Kim, N. D."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". International Journal of Oncology 51.2 (2017): 715-723.
Chicago
Kim, D. H., Sung, B., Kim, J., Kang, Y. J., Hwang, S. Y., Hwang, N., Suh, H., Choi, Y. H., Im, E., Chung, H. Y., Kim, N. D."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". International Journal of Oncology 51, no. 2 (2017): 715-723. https://doi.org/10.3892/ijo.2017.4058