title: Ligularia fischeri inhibits endothelial cell proliferation, invasion and tube formation through the inactivation of mitogenic signaling pathways and regulation of vascular endothelial cadherin distribution and matrix metalloproteinase expression.
abstract: Ligularia fischeri (LF) has been used as an edible herb and traditional medicine for the treatment of inflammatory and infectious diseases. In the present study, we report the effects and molecular mechanism of the ethanolic extract of LF on cell proliferation, invasion and tube formation in human umbilical vein endothelial cells (HUVECs). LF-mediated inhibition of cell proliferation was accompanied by reduced expression of cell cycle-related proteins such as cyclin-dependent kinases (Cdks) and cyclins, leading to pRb hypophosphorylation and G1 phase cell cycle arrest. We also show that LF treatment inhibited cell invasion and tube formation in HUVECs. These anti-angiogenic activities of LF were associated with the inactivation of mitogenic signaling pathways, induction of vascular endothelial (VE)-cadherin distribution at cell-cell contacts and inhibition of matrix metalloproteinase (MMP) expression. Collectively, our findings demonstrate the pharmacological functions and molecular mechanisms of LF in regulating endothelial cell fates, and support further development as a potential therapeutic agent for the treatment and prevention of angiogenesis-related disorders including cancer.
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Hyeon-Ju
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Natural Products Research Institute, Gyeonggi Institute of Science and Technology Promotion, Suwon 443‑270, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Natural Products Research Institute, Gyeonggi Institute of Science and Technology Promotion, Suwon 443‑270, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Ahn
authors.affiliation: Natural Products Research Institute, Gyeonggi Institute of Science and Technology Promotion, Suwon 443‑270, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: Natural Products Research Institute, Gyeonggi Institute of Science and Technology Promotion, Suwon 443‑270, Republic of Korea.
authors.forename: Young-Rak
authors.initials: YR
authors.lastname: Cho
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Sang-Jin
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.affiliation: Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Park
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Joa Sub
authors.initials: JS
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D019659:Asteraceae / Q000737:chemistry; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D010936:Plant Extracts / Q000008:administration & dosage* / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D020782:Matrix Metalloproteinases; D010936:Plant Extracts; D000099152:Cadherin 5