Curcumin suppresses cell proliferation through inhibition of the Wnt/β-catenin signaling pathway in medulloblastoma

被引:69
作者
He, Misi [1 ]
Li, Yu [2 ]
Zhang, Li [1 ]
Li, Longjiang [1 ]
Shen, Yi [1 ]
Lin, Ling [1 ]
Zheng, Weiping [3 ]
Chen, Li [3 ]
Bian, Xiuwu [4 ,5 ]
Ng, Ho-Keung [6 ]
Tang, Li [1 ]
机构
[1] Chongqing Med Univ, Dept Pathophysiol, Chongqing 400016, Peoples R China
[2] Chongqing Med Univ, Inst Neurosci, Dept Pathol, Chongqing 400016, Peoples R China
[3] Chongqing Med Univ, Expt & Teaching Ctr, Chongqing 400016, Peoples R China
[4] Third Mil Med Univ, Inst Pathol, Chongqing, Peoples R China
[5] Third Mil Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing, Peoples R China
[6] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China
基金
美国国家科学基金会;
关键词
medulloblastoma; Wnt signaling pathway; beta-catenin; curcumin; IN-VIVO; GROWTH; CANCER; ANGIOGENESIS; PHOSPHORYLATION; ACTIVATION; APOPTOSIS; DISEASE; GSK3;
D O I
10.3892/or.2014.3206
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Recently, the survival rate of medulloblastoma patients has greatly improved; yet, patients undergoing current treatment regimes suffer from serious therapy-related side-effects. The aim of the present study was to investigate the anticancer effects of curcumin on medulloblastoma cells by testing its capacity to suppress proliferation and regulate the Wnt/beta-catenin pathway. In the present study, cell proliferation was determined by MTT assay. Cell cycle was observed by flow cytometry. The changes in the Wnt/beta-catenin pathway were analyzed by immunofluorescence, western blot analysis and RT-PCR. Curcumin treatment resulted in a dose- and time-dependent inhibition of proliferation in the medulloblastoma cell line. Curcumin treatment arrested the cell-cycle at the G(2)/M phase. Furthermore, curcumin treatment led to activation of GSK-3 beta, reduced expression of beta-catenin and its downstream target cyclin D1. The attenuation of the Wnt/beta-catenin pathway was due to the loss of nuclear P-catenin. In conclusion, curcumin can inhibit cell growth by suppressing the Wnt/beta-catenin signaling pathway, and it has the potential to be developed as a therapeutic agent for medulloblastoma.
引用
收藏
页码:173 / 180
页数:8
相关论文
共 36 条
[1]
Curcumin and cancer: An "old-age" disease with an "age-old" solution [J].
Anand, Preetha ;
Sundaram, Chitra ;
Jhurani, Sonia ;
Kunnumakkara, Ajaikumar B. ;
Aggarwal, Bharat B. .
CANCER LETTERS, 2008, 267 (01) :133-164
[2]
Proximal events in Wnt signal transduction [J].
Angers, Stephane ;
Moon, Randall T. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2009, 10 (07) :468-477
[3]
Medulloblastoma A disease with disorganized developmental signaling cascades [J].
Baryawno, Ninib ;
Sveinbjornsson, Baldur ;
Kogner, Per ;
Johnsen, John Inge .
CELL CYCLE, 2010, 9 (13) :2548-2554
[4]
Small-Molecule Inhibitors of Phosphatidylinositol 3-Kinase/Akt Signaling Inhibit Wnt/β-Catenin Pathway Cross-Talk and Suppress Medulloblastoma Growth [J].
Baryawno, Ninib ;
Sveinbjornsson, Baldur ;
Eksborg, Staffan ;
Chen, Ching-Shih ;
Kogner, Per ;
Johnsen, John Inge .
CANCER RESEARCH, 2010, 70 (01) :266-276
[5]
Norcantharidin impairs medulloblastoma growth by inhibition of Wnt/β-catenin signaling [J].
Cimmino, Flora ;
Scoppettuolo, Maria Nunzia ;
Carotenuto, Marianeve ;
De Antonellis, Pasqualino ;
Di Dato, Valeria ;
De Vita, Gennaro ;
Zollo, Massimo .
JOURNAL OF NEURO-ONCOLOGY, 2012, 106 (01) :59-70
[6]
Cole GM, 2007, ADV EXP MED BIOL, V595, P197
[7]
Biological background of pediatric medulloblastoma and ependymoma: A review from a translational research perspective [J].
de Bont, Judith M. ;
Packer, Roger J. ;
Michiels, Erna M. ;
den Boer, Monique L. ;
Pieters, Rob .
NEURO-ONCOLOGY, 2008, 10 (06) :1040-1060
[8]
Dorai T, 2001, PROSTATE, V47, P293, DOI 10.1002/pros.1074
[9]
Curcumin Inhibits the Sonic Hedgehog Signaling Pathway and Triggers Apoptosis in Medulloblastoma Cells [J].
Elamin, Maha H. ;
Shinwari, Zakia ;
Hendrayani, Siti-Faujiah ;
Al-Hindi, Hindi ;
Al-Shail, Essam ;
Khafaga, Yasser ;
Al-kofide, Amani ;
Aboussekhra, Abdelilah .
MOLECULAR CARCINOGENESIS, 2010, 49 (03) :302-314
[10]
A common phosphate binding site explains the unique substrate specificity of GSK3 and its inactivation by phosphorylation [J].
Frame, S ;
Cohen, P ;
Biondi, RM .
MOLECULAR CELL, 2001, 7 (06) :1321-1327