Abstract 203: Pseudosemiglabrin inhibits tumor angiogenesis and tumor growth of human colon cancer in xenograft mouse models by downregulating endothelial functions, Notch and VEGF pathways

Abstract

Abstract Many antineoplasic agents were identified from natural product. One such agent is (-)-pseudosemiglabrin extracted from aerial parts of Tephrosia apollinea, while significant progress has been made in understanding the antineoplasic and anti-inflammatory of prenylated flavone (-)-pseudosemiglabrin (SSG), little is known about its antiangiogenic and antitumor in vivo. Using rat aortic ring assay and zebrafish model, SSG dramatically suppressed angiogenesis in vitro, ex vivo and in vivo models, SSG profoundly inhibited the outgrowth of new vessels from explants rat aortic ring, moreover it impaired human endothelial cells (HUVEC) migration and formation of capillary-like structure in vitro in none toxic doses. In this study we hypothesize that SSG can hampered tumor angiogenesis and tumor growth of colorectal cancer in ectopically and orthotopically implanted in nude mice, oral administration of SSG (25- 100mg/kg) significantly inhibited colon tumors growth in nude mice. Histological and Immunohistochemistry analysis further revealed that the stained blood vessels and expression of CD31 in xenograft were remarkably decreased in tumors excised from animals treated with SSG. Mechanistically the compound inhibits tumor angiogenesis by downregulation of Notch downstream (NCID); also SSG was found to inhibit VEGF secretion from human cancer cells as well as endothelial cells. In conclusion, the results demonstrated an original role of (-)-pseudosemiglabrin in inhibiting tumor angiogenesis and tumor growth via inhibition Notch and VEGF pathways. This study also validates the central role of Notch in tumor angiogenesis and suggests that (-)-pseudosemiglabrin could be a potential therapeutic candidate for cancer and other angiogenesis related diseases. Note: This abstract was not presented at the meeting. Citation Format: Loiy E. Ahmed Hassan, Azman Seeni, Amin M. Abdul Majid. Pseudosemiglabrin inhibits tumor angiogenesis and tumor growth of human colon cancer in xenograft mouse models by downregulating endothelial functions, Notch and VEGF pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 203.