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DOI: 10.1055/s-0032-1320441
Anti-angiogenesis and immunomodulatory activities of an anti-tumor sesquiterpene bigelovin
Bigelovin is a sesquiterpene lactone isolated from the plant Inula helianthus-aquatica which was traditionally used in cancer treatment in Yunnan, China. We previously demonstrated the potent apoptotic activities of bigelovin. The objective of this study was to investigate the anti-angiogenic and immunomodulatory effects of bigelovin using transgenic zebrafish Tg(fli1a:EGFP)y1 with fluorescent blood vessels and human peripheral blood mononuclear cells (PBMCs), respectively. The growth of subintestinal vessels and gene expression in angiogenesis signaling pathways of bigelovin-treated zebrafish embryos were examined. The proliferation and cytokines production of bigelovin-treated PBMCs were also evaluated. Our results showed that bigelovin could significantly inhibit the growth of subintestinal vessels and down-regulate the expression of Ang2 and Tie2 of zebrafish embryos. Besides, bigelovin could significantly suppress the proliferation and production of Th1 cytokines (IFNγ, IL-2 and IL-12) in human PBMCs. This is the first report of the anti-angiogenic and immunomodulatory activities of bigelovin in zebrafish and human lymphocytes. Our findings suggest that bigelovin may exert multi-target function against tumor in animal model.