title: Apigenin Attenuates Melanoma Cell Migration by Inducing Anoikis through Integrin and Focal Adhesion Kinase Inhibition.
abstract: Apigenin, a nonmutagenic flavonoid, has been found to have antitumor properties and is therefore particularly relevant for the development of chemotherapeutic agents for cancers. In this study, time- and dose-dependent cell viability and cytotoxicity were assessed to determine the effects of apigenin on A2058 and A375 melanoma cells. Melanoma cells were pretreated with different concentrations of apigenin and analyzed for morphological changes, anoikis induction, cell migration, and levels of proteins associated with apoptosis. Apigenin reduced integrin protein levels and inhibited the phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK1/2), which induce anoikis in human cutaneous melanoma cells. Apigenin exhibited dose-dependent inhibition of melanoma cell migration, unlike untreated controls. Furthermore, apigenin treatment increased apoptotic factors such as caspase-3 and cleaved poly(ADP-ribose) polymerase in a dose-dependent manner, demonstrating the metastasis of melanoma cells. Our results provide a new insight into the mechanisms by which apigenin prevents melanoma metastasis by sensitizing anoikis induced by the loss of integrin proteins in the FAK/ERK1/2 signaling pathway. These findings elucidate the related mechanisms and suggest the potential of apigenin in developing clinical treatment strategies against malignant melanoma.
authors.affiliation: Department of Life Sciences, College of Biomedical &amp; Health Science, Konkuk University, Chungju 380-701, Korea. noman33ju@gmail.com.
authors.forename: Md Abul
authors.initials: MA
authors.lastname: Hasnat
authors.affiliation: Department of Life Sciences, College of Biomedical &amp; Health Science, Konkuk University, Chungju 380-701, Korea. mehnaz.pervin@gmail.com.
authors.forename: Mehnaz
authors.initials: M
authors.lastname: Pervin
authors.affiliation: Department of Life Sciences, College of Biomedical &amp; Health Science, Konkuk University, Chungju 380-701, Korea. jhlim@kku.ac.kr.
authors.forename: Ji Hong
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Department of Life Sciences, College of Biomedical &amp; Health Science, Konkuk University, Chungju 380-701, Korea. beongou@kku.ac.kr.
authors.forename: Beong Ou
authors.initials: BO
authors.lastname: Lim
mesh_terms: D023102:Anoikis / Q000187:drug effects*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D016023:Integrins; D012333:RNA, Messenger; D047310:Apigenin; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: anoikis; apigenin; integrin-FAK signaling; melanoma; migration