title: Berberine suppressed epithelial mesenchymal transition through cross-talk regulation of PI3K/AKT and RARα/RARβ in melanoma cells.
abstract: Berberine is a natural compound extracted from Coptidis rhizoma, and accumulating proof has shown its potent anti-tumor properties with diverse action on melanoma cells, including inhibiting cancer viability, blocking cell cycle and migration. However, the mechanisms of berberine have not been fully clarified. In this study, we identified that berberine reduced the migration and invasion capacities of B16 cells, and notably altered pluripotency of epithelial to mesenchymal transition associated factors. We found that berberine also downregulation the expression level of p-PI3K, p-AKT and retinoic acid receptor α (RARα) and upregulation the expression level of retinoic acid receptor β and γ (RARβ and RARγ). These effects of PI3 kinase inhibitor LY294002 treatment mimicked Berberine treatment except the expression level of RARγ. Moreover, Western blot analysis showed that the decreased PI3K and AKT phosphorylation, increased the epithelial maker E-cadherin, and upregulation level of RARβ while decreased the mesenchymal markers N-cadherin and downregulation level of RARα by incubation with LY294002 in mouse melanoma B16 cells. In conclusion, Our study reveal that berberine can reverse the epithelial to mesenchymal transition of mouse melanoma B16 cells and may be a useful adjuvant therapeutic agent in the treatment of melanoma through the PI3K/Akt pathway and inactivation PI3K/AKT could regulate RARα/RARβ expression.
authors.affiliation: Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kou
authors.affiliation: Henan Institute of Orthopedic and Traumatology, Henan Luoyang Orthopedic-Traumatological Hospital, Henan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: dubiaoyan@gzucm.edu.cn.
authors.forename: Biaoyan
authors.initials: B
authors.lastname: Du
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D001599:Berberine / Q000737:chemistry*; D002867:Chromones / Q000737:chemistry; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic; D008545:Melanoma / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D009025:Morpholines / Q000737:chemistry; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012878:Skin Neoplasms / Q000188:drug therapy*; D014945:Wound Healing
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D009025:Morpholines; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; C082925:retinoic acid receptor beta; D001599:Berberine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Berberine; Epithelial mesenchymal transition; Melanoma; PI3K/AKT; Retinoic acid receptor