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Oncol Rep ; 40(5): 3024-3032, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30132559

ABSTRACT

Morin is a naturally occurring bioflavonoid originally isolated from members of the Moraceae family of flowering plants and it possesses antitumor activity in various human cancer cells. The present study explored the antitumor effects of morin in tongue squamous cell carcinoma (TSCC) cells in vitro and investigated the underlying molecular events. A TSCC cell line was treated with different doses of morin for up to 48 h. Analyses of cell viability, using Cell Counting Kit­8 (CCK­8), EdU incorporation, colony formation, flow cytometric analysis of cell cycle distribution and apoptosis, wound healing assay, western blot analysis and qRT­PCR assays, were then performed. The data revealed that morin treatment reduced Cal27 cell proliferation and reduced the migration capacity of tumor cells in a dose­dependent manner. Morin treatment also significantly upregulated mammalian sterile 20­like 1 (MST1) and MOB kinase activator 1 (MOB1) phosphorylation in CAL27 cells, but suppressed nuclear translocation of yes­associated protein (YAP) through the induction of YAP phosphorylation in Cal27 cells. Moreover, the expression of YAP­targeting genes, such as CTGF, CYR61 and ANKRD, was downregulated in morin­treated TSCC cells, indicating that morin was able to activate the Hippo signaling pathway to inhibit YAP nuclear translocation and YAP­related transcriptional activity in TSCC cells. In conclusion, the data from the present study demonstrated that morin produces anti­TSCC activity in vitro through activation of the Hippo signaling pathway and the downstream suppression of YAP activity in TSCC cells. Future studies should assess the clinical antitumor effects of morin.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Squamous Cell/drug therapy , Flavonoids/pharmacology , Head and Neck Neoplasms/drug therapy , Plant Extracts/pharmacology , Tongue Neoplasms/drug therapy , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Cell Cycle Proteins , Cell Line, Tumor , Cell Movement/drug effects , Cell Nucleus/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , Down-Regulation/drug effects , Drug Screening Assays, Antitumor , Flavonoids/therapeutic use , Hippo Signaling Pathway , Humans , Moraceae/chemistry , Nuclear Proteins/metabolism , Plant Extracts/therapeutic use , Protein Serine-Threonine Kinases/metabolism , Signal Transduction/drug effects , Squamous Cell Carcinoma of Head and Neck , Transcription Factors/metabolism , Up-Regulation/drug effects
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