title: A synthetic isoflavone, DCMF, promotes human keratinocyte migration by activating Src/FAK signaling pathway.
abstract: Flavonoids are plant secondary compounds with various pharmacological properties. We previously showed that one flavonoid, trimethoxyisoflavone (TMF), could promote wound healing by inducing keratinocyte migration. Here, we screened TMF derivatives for enhanced activity and identified one compound, 2',6 Dichloro-7-methoxyisoflavone (DCMF), as most effective at promoting migration in a scratch wound assay. Using the HaCaT keratinocyte cell line, we found DCMF treatment induced phosphorylation of both FAK and Src, and increased keratinocyte migration. DCMF-induced Src kinase could promote activation of ERK, AKT, and p38 signaling pathways, and DCMF-induced secretion of matrix metalloproteinase (MMP)-2 and MMP-9 and partial epithelial-mesenchymal transition (EMT), whereas Src inhibition abolished DCMF-induced EMT. Using an in vivo excisional wound model, we observed improved wound closure and re-epithelialization in DCMF-treated mice, as compared to controls. Collectively, our data demonstrate that DCMF induces cell migration and promotes wound healing through activation of Src/FAK, ERK, AKT, and p38 MAPK signaling.
authors.affiliation: Department of Biochemistry, School of Medicine, Jeju National University, Republic of Korea.
authors.forename: Phorl
authors.initials: P
authors.lastname: Sophors
authors.affiliation: Department of Biochemistry, School of Medicine, Jeju National University, Republic of Korea.
authors.forename: Young Mee
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Medicine, Jeju National University, Republic of Korea.
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Seo
authors.affiliation: Jeju Regional Cancer Center, Jeju National University Hospital, Republic of Korea.
authors.forename: Jung-Sik
authors.initials: JS
authors.lastname: Huh
authors.affiliation: Division of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Yoongho
authors.initials: Y
authors.lastname: Lim
authors.affiliation: Department of Applied Chemistry, Dongduk Women's University, Seoul 136-714, Republic of Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Koh
authors.affiliation: Department of Biochemistry, School of Medicine, Jeju National University, Republic of Korea; Jeju Regional Cancer Center, Jeju National University Hospital, Republic of Korea; Institute of Medical Science, Jeju National University, Republic of Korea. Electronic address: moonjcho@jejunu.ac.kr.
authors.forename: Moonjae
authors.initials: M
authors.lastname: Cho
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage* / Q000138:chemical synthesis; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D007529:Isoflavones; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases
keywords: Cell migration; Flavonoid; Keratinocytes; Wound healing