title: Curcumin suppresses cell growth and invasion and induces apoptosis by down-regulation of Skp2 pathway in glioma cells.
abstract: Studies have demonstrated that curcumin exerts its tumor suppressor function in a variety of human cancers including glioma. However, the exact underlying molecular mechanisms remain obscure. Emerging evidence has revealed that Skp2 (S-phase kinase associated protein 2) plays an oncogenic role in tumorigenesis. Therefore, we aim to determine whether curcumin suppresses the Skp2 expression, leading to the inhibition of cell growth, invasion, induction of apoptosis, and cell cycle arrest. To this end, we conducted multiple methods such as MTT assay, Flow cytometry, Wound healing assay, invasion assay, RT-PCR, Western blotting, and transfection to explore the functions and molecular insights of curcumin in glioma cells. We found that curcumin significantly inhibited cell growth, suppressed cell migration and invasion, induced apoptosis and cell cycle arrest in glioma cells. Furthermore, we observed that overexpression of Skp2 promoted cell growth, migration, and invasion, whereas depletion of Skp2 suppressed cell growth, migration, and invasion and triggered apoptosis in glioma cells. Mechanistically, we defined that curcumin markedly down-regulated Skp2 expression and subsequently up-regulated p57 expression. Moreover, our results demonstrated that curcumin exerts its antitumor activity through inhibition of Skp2 pathway. Collectively, our findings suggest that targeting Skp2 by curcumin could be a promising therapeutic approach for glioma prevention and therapy.
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Xiantao
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xingming
authors.initials: X
authors.lastname: Cai
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Jingna
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of ENT, Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Renqiang
authors.initials: R
authors.lastname: Ma
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Xuyuan
authors.initials: X
authors.lastname: Yin
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Xiuxia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Geriatrics, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.|Department of ENT, Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Huabin
authors.initials: H
authors.lastname: Li
authors.affiliation: The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Jiangsu Institute of Hematology, The First Affiliated Hospital, Soochow University, Suzhou, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57; D044786:S-Phase Kinase-Associated Proteins; D003474:Curcumin
keywords: Skp2; curcumin; glioma; growth; invasion