title: Reduction of COX-2 through modulating miR-124/SPHK1 axis contributes to the antimetastatic effect of alpinumisoflavone in melanoma.
abstract: Alpinumisoflavone (AIF) is a naturally occurring flavonoid that is a major bioactive component of the medicinal plantDerris eriocarpa. In this study we evaluated the antimetastatic effect of AIF and investigated the underlying mechanism of action usingin vitroandin vivomodels of melanoma. We found that AIF impaired the metastatic potential of A375 and SK-MEL-1 human melanoma cells by promoting cell differentiation as assessed by melanin content, protoporphyrin IX accumulation, and tissue transglutaminase activity. In addition, AIF inhibited cell adhesion, migration, and invasion in melanoma cells. We found that AIF treatment decreased cyclooxygenase-2 (COX-2) expression, and COX-2 overexpression attenuated the inhibitory effects of AIF on the metastatic behaviors of melanoma cells. AIF dose-dependently increased microRNA-124 (miR-124) levels and decreased levels of sphingosine kinase 1 (SPHK1), a target of miR-124. In a mouse model of melanoma, AIF suppressed lung metastasis. Taken together, our findings suggest that AIF inhibits metastasis in melanoma by modulating COX-2 expression, at least in part, through targeting the miR-124/SphK1 axis. Our study provides evidence that AIF may be useful as an antimetastatic agent in the treatment of melanoma.
authors.affiliation: Department of Dermatology, Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang 471000, Henan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Dermatology, Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang 471000, Henan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Dermatology, Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang 471000, Henan, China.
authors.forename: Xiuyong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang 471000, Henan, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ban
authors.affiliation: Department of Dermatology, Luoyang Central Hospital Affiliated to Zhengzhou University Luoyang 471000, Henan, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
keywords: Alpinumisoflavone; COX-2; SPHK1; melanoma; metastasis; miR-124