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

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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.

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.