Anti-angiogenesis and immunomodulatory activities of an anti-tumor sesquiterpene bigelovin isolated from Inula helianthus-aquatica.

Abstract

Bigelovin is a sesquiterpene lactone isolated from the plant Inula helianthus-aquatica which was traditionally used in cancer treatment in Yunnan, China. The potent apoptotic activities of bigelovin in human leukemia U937 cells were shown in our previous study. The present study investigated 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. Furthermore, the inhibitory activities of bigelovin on the human endothelial cell adhesion molecules (CAMs) were also examined. Our results showed that the growth of subintestinal vessels of the bigelovin-treated zebrafish embryos was significantly inhibited and the gene expressions in angiogenesis signaling pathways (e.g. Ang2 and Tie2) of the zebrafish were down-regulated after bigelovin treatment. Besides, the proliferation and Th1 cytokines productions (e.g. IFN-γ, IL-2 and IL-12) were suppressed in bigelovin-treated PBMCs. On the other hand, bigelovin was shown to significantly inhibit the human monocyte adhesion to human endothelial cells and the gene expressions of inflammation-related CAMs (e.g. ICAM-1, VCAM-1 and E-selectin) were significantly down-regulated in bigelovin-treated human endothelial cells. In summary, our data provide the first evidence that bigelovin possesses anti-angiogenic and immunomodulatory activities, suggesting bigelovin may exert multi-target functions against cancer in animal models.

• Authors: Grace G L Yue, Ben C L Chan, Hin-Fai Kwok, Yuk-Lau Wong, Hoi-Wing Leung, Chang-Jiu Ji, Kwok-Pui Fung, Ping-Chung Leung, Ning-Hua Tan, Clara B S Lau
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 59 Pg. 243-52 (Jan 2013) ISSN: 1768-3254 [Electronic] France
• PMID: 23231968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Immunologic Factors
• Lactones
• Plant Extracts
• Sesquiterpenes
• bigelovin

Topics

• Animals
• Animals, Genetically Modified
• Antineoplastic Agents (chemistry, pharmacology)
• China
• Embryo, Nonmammalian (drug effects)
• Gene Expression Regulation (drug effects)
• Helianthus (chemistry)
• Humans
• Immunologic Factors (chemistry, pharmacology)
• Lactones (chemistry, isolation & purification, pharmacology)
• Neovascularization, Physiologic (drug effects)
• Plant Extracts (isolation & purification, pharmacology)
• Plant Leaves (chemistry)
• Sesquiterpenes (chemistry, isolation & purification, pharmacology)
• U937 Cells
• Zebrafish