title: Widdrol, a sesquiterpene isolated from Juniperus chinensis, inhibits angiogenesis by targeting vascular endothelial growth factor receptor 2 signaling.
abstract: Widdrol is an odorous compound derived from Juniperus chinensis that is widely used in traditional medicine to treat fever, inflammation and cancer. It was previously reported that widdrol has antitumor activity by apoptosis induction in cancer cells in vitro. However, its anti-angiogenic activity remains elusive. In the present study, we investigated the anti‑angiogenic activity of widdrol and the molecular mechanisms involved. Widdrol inhibited cell proliferation via G1 phase arrest induction in human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Additionally, it was associated with a decreased expression of cyclin-dependent kinase 2 (CDK2) and an increased expression of p21, a CDK inhibitor. Widdrol significantly inhibited the cell migration and tube formation of HUVECs using an in vitro angiogenesis assay. The results showed that widdrol suppressed phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) and its downstream proteins, such as AKT, focal adhesion kinase (FAK) and endothelial nitric oxide synthase (eNOS). Moreover, widdrol effectively reduced tumor growth and blood vessel formation in colon tumor xenograft mice. Collectively, these results suggested that widdrol may act as a potential anti-angiogenic agent by inhibiting vessel sprouting and growth, which may have implications for angioprevention.
authors.affiliation: Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea.
authors.forename: Soojung
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Yun
authors.affiliation: Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea.
authors.forename: Hyun Young
authors.initials: HY
authors.lastname: Jeong
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea.
authors.forename: You Na
authors.initials: YN
authors.lastname: Oh
authors.affiliation: Blue-Bio Industry Regional Innovation Center, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea.
authors.forename: Seung-Geun
authors.initials: SG
authors.lastname: Yun
authors.affiliation: Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea.
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.affiliation: Department of Life Science and Biotechnology, College of Natural Sciences and Human Ecology, Dong-Eui University, Busanjin-gu, Busan 614-714, Republic of Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Kwon
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001567:Benzocycloheptenes / Q000494:pharmacology*; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D018653:Juniperus / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D001567:Benzocycloheptenes; D010936:Plant Extracts; C078670:widdrol; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2