title: Marmesin-mediated suppression of VEGF/VEGFR and integrin β1 expression: Its implication in non-small cell lung cancer cell responses and tumor angiogenesis.
abstract: In the present study, we investigated the effects and molecular mechanism of marmesin, a natural coumarin compound isolated from Broussonetia kazinoki, on non-small cell lung cancer (NSCLC) cell responses and tumor angiogenesis. Marmesin abrogated mitogen-stimulated proliferation and invasion in both p53 wild-type A549 and p53-deficient H1299 NSCLC cells. These antitumor activities of marmesin were mediated by the inactivation of mitogenic signaling pathways and downregulation of cell signaling-related proteins including vascular endothelial growth factor receptor-2 (VEGFR-2), integrin β1, integrin-linked kinase and matrix metalloproteinases-2. Furthermore, marmesin suppressed the expression and secretion of VEGF in both NSCLC cells, leading to inhibition of capillary-like structure formation in human umbilical vein endothelial cells. Collectively, these findings demonstrate the pharmacological roles and molecular targets of marmesin in regulating NSCLC cell responses and tumor angiogenesis.
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.
authors.forename: Jae Hyeon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.
authors.forename: Min Su
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.
authors.forename: Bo Hee
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Biocenter, Gyeonggi Institute of Science and Technology Promotion, Suwon 16229, Republic of Korea.
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Biocenter, Gyeonggi Institute of Science and Technology Promotion, Suwon 16229, Republic of Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Ahn
authors.affiliation: Biocenter, Gyeonggi Institute of Science and Technology Promotion, Suwon 16229, Republic of Korea.
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Ko
authors.affiliation: Biocenter, Gyeonggi Institute of Science and Technology Promotion, Suwon 16229, 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 04310, 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 04310, 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 04310, Republic of Korea.
authors.forename: Yong Kee
authors.initials: YK
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.
authors.forename: Joa Sub
authors.initials: JS
authors.lastname: Oh
authors.affiliation: College of Pharmacy, Dankook University, Cheonan 31116, Republic of Korea.
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
mesh_terms: D000072283:A549 Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics*; D008175:Lung Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D003374:Coumarins; D019012:Integrin beta1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; C001684:marmesin