Sonic hedgehog and Wnt/-catenin pathways mediate curcumin inhibition of breast cancer stem cells

被引：6

作者：

Li, Xiaoting ^{[1
,2
]}

Wang, Xiaoqian ^{[1
]}

Xie, Chunfeng ^{[1
,2
]}

Zhu, Jianyun ^{[1
]}

Meng, Yu ^{[1
]}

Chen, Yue ^{[1
]}

Li, Yuan ^{[1
]}

Jiang, Ye ^{[1
]}

Yang, Xue ^{[1
]}

Wang, Shijia ^{[1
]}

Chen, Jiaqi ^{[1
]}

Zhang, Qi ^{[1
]}

Geng, Shanshan ^{[1
,2
]}

Wu, Jieshu ^{[1
,2
]}

Zhong, Caiyun ^{[1
,2
]}

Zhao, Yu ^{[3
]}

机构：

[1] Nanjing Med Univ, Dept Nutr & Food Safety, Nanjing, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Key Lab Modern Toxicol, Minist Educ, Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China

[3] Nanjing Med Univ, Sch Clin Med 1, Dept Med Imaging, 818 East Tianyuan Rd, Nanjing 211166, Jiangsu, Peoples R China

来源：

ANTI-CANCER DRUGS | 2018年 / 29卷 / 03期

基金：

中国国家自然科学基金;

关键词：

breast cancer stem cells; curcumin; inhibition; sonic hedgehog pathway; Wnt; -catenin pathway; SIGNALING PATHWAY; PROGENITOR CELLS; ACTIVATION; POOR; PROLIFERATION; PURMORPHAMINE; TRANSDUCTION; EXPRESSION; TARGET; TUMORS;

D O I：

10.1097/CAD.0000000000000584

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer stem cells (CSCs) play an essential role in the progression of many tumors. Sonic hedgehog (Shh) and Wnt/-catenin pathways are crucial in maintaining the stemness of CSCs. Curcumin has been shown to possess anticancer activity. However, the interventional effect of curcumin on breast CSCs has not been elucidated. In the present study, we investigated the role of Shh and Wnt/-catenin pathway in curcumin inhibition of breast CSCs. We showed that the levels of breast CSCs markers were significantly elevated in SUM159 and MCF7 sphere-forming cells. We further illustrated that curcumin effectively decreased breast CSCs activity by inhibiting tumor sphere formation, decreasing breast CSCs markers (CD44, ALDH1A1, Nanog, and Oct4), as well as inhibiting proliferation and inducing apoptosis. Moreover, we showed that downregulation of Shh and Wnt/-catenin activity resulted in breast CSCs inhibition; curcumin exerted an inhibitory effect on breast CSCs by suppressing both Shh and Wnt/-catenin pathways. Taken together, these results indicated curcumin inhibition of breast CSCs by downregulation of Shh and Wnt/-catenin pathways. Findings from this study could provide new insights into the potential therapeutic application of curcumin in breast CSCs elimination and cancer intervention.

引用

页码：208 / 215

页数：8

共 47 条

[1] Targeting Inflammation-Induced Obesity and Metabolic Diseases by Curcumin and Other Nutraceuticals [J].

Aggarwal, Bharat B. .

ANNUAL REVIEW OF NUTRITION, VOL 30, 2010, 30 :173-199

[2] Curcumin downregulates the inflammatory cytokines CXCL1 and-2 in breast cancer cells via NFκB [J].

Bachmeier, Beatrice E. ;

Mohrenz, Isabelle V. ;

Mirisola, Valentina ;

Schleicher, Erwin ;

Romeo, Francesco ;

Hoehneke, Clara ;

Jochum, Marianne ;

Nerlich, Andreas G. ;

Pfeffer, Ulrich .

CARCINOGENESIS, 2008, 29 (04) :779-789

[3] The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice [J].

Bachmeier, Beatrice E. ;

Nerlich, Andreas G. ;

Iancu, Cristina M. ;

Cilli, Michele ;

Schleicher, Erwin ;

Vene, Roberta ;

Dell'Eva, Raffaella ;

Jochum, Marianne ;

Albini, Adriana ;

Pfeffer, Ulrich .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2007, 19 (1-4) :137-152

[4] Targeting constitutive and interleukin-6-inducible signal transducers and activators of transcription 3 pathway in head and neck squamous cell carcinoma cells by curcumin (diferuloylmethane) [J].

Chakravarti, Nitin ;

Myers, Jeffrey N. ;

Aggarwal, Bharat B. .

INTERNATIONAL JOURNAL OF CANCER, 2006, 119 (06) :1268-1275

[5] Activated Wnt/β-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model [J].

Chien, Andy J. ;

Moore, Erin C. ;

Lonsdorf, Anke S. ;

Kulikauskas, Rima M. ;

Rothberg, Bonnie Gould ;

Berger, Aaron J. ;

Major, Michael B. ;

Hwang, Sam T. ;

Rimm, David L. ;

Moon, Randall T. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (04) :1193-1198

[6] In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells [J].

Dontu, G ;

Abdallah, WM ;

Foley, JM ;

Jackson, KW ;

Clarke, MF ;

Kawamura, MJ ;

Wicha, MS .

GENES & DEVELOPMENT, 2003, 17 (10) :1253-1270

[7] Sonic Hedgehog-dependent proliferation in a series of patients with colorectal cancer [J].

Douard, R ;

Moutereau, S ;

Pernet, P ;

Chimingqi, M ;

Allory, Y ;

Manivet, P ;

Conti, M ;

Vaubourdolle, M ;

Cugnenc, PH ;

Loric, S .

SURGERY, 2006, 139 (05) :665-670

[8] Cooperatively transcriptional and epigenetic regulation of sonic hedgehog overexpression drives malignant potential of breast cancer [J].

Duan, Zhao-Heng ;

Wang, Hao-Chuan ;

Zhao, Dong-Mei ;

Ji, Xiao-Xin ;

Song, Min ;

Yang, Xiao-Jun ;

Cui, Wei .

CANCER SCIENCE, 2015, 106 (08) :1084-1091

[9] Curcumin inhibits the side population (SP) phenotype of the rat C6 glioma cell line: Towards targeting of cancer stem cells with phytochemicals [J].

Fong, Dunne ;

Yeh, Arthur ;

Naftalovich, Rotem ;

Choi, Theresa Hyejeong ;

Chan, Marion M. .

CANCER LETTERS, 2010, 293 (01) :65-72

[10] ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome [J].

Ginestier, Christophe ;

Hur, Min Hee ;

Charafe-Jauffret, Emmanuelle ;

Monville, Florence ;

Dutcher, Julie ;

Brown, Marty ;

Jacquemier, Jocelyne ;

Viens, Patrice ;

Kleer, Celina G. ;

Liu, Suling ;

Schott, Anne ;

Hayes, Dan ;

Birnbaum, Daniel ;

Wicha, Max S. ;

Dontu, Gabriela .

CELL STEM CELL, 2007, 1 (05) :555-567

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