Niclosamide Suppresses Proliferation, Induces Apoptosis and Inhibits Wnt/β-catenin Signaling Pathway in Human Ovarian Cancer Cells

被引:0
作者
Gundogdu, Ayse Cakir [1 ]
Kaplanoglu, Gulnur Take [1 ]
Sivas, Hulya [2 ]
Varol, Reyhan [2 ]
Seymen, Cemile Merve [1 ]
机构
[1] Gazi Univ, Fac Med, Dept Histol & Embryol, TR-06500 Ankara, Turkey
[2] Anadolu Univ, Fac Sci, Dept Biol, Eskisehir, Turkey
来源
GAZI MEDICAL JOURNAL | 2019年 / 30卷 / 02期
关键词
OVCAR-3; niclosamide; 5-fluorouracil; Wnt/beta-catenin; proliferation; apoptosis; MECHANISMS; ERLOTINIB; PROTEINS; ANALOGS; GROWTH; STAT3;
D O I
10.12996/gmj.2019.43
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: The aim of this study is to investigate in vitro effects of an antihelminthic drug niclosamide on human ovarian carcinoma cell line OVCAR3. Methods: MTT assay was applied to investigate the cytotoxic effects of niclosamide on the cells. beta-catenin levels in the cells were analyzed by immunocytochemistry, in order to assess the potency of niclosamide on Wnt/beta-catenin signaling pathway that function in cell proliferation. The effects of the drug on apoptosis were detected by TUNEL method. All the assays were also performed for chemotherapy agent 5-fluorouracil (5-FU) and anticancer effects of these two drugs were compared. Results: It was found that niclosamide at 1 mu M and 2 mu M concentrations reduced cell viability, whereas 5-FU showed its significant proliferation inhibitory effect at higher concentrations. Niclosamide led to an increase in apoptosis while this effect was weaker compared with 5-FU. Niclosamide treatment decreased beta-catenin staining in the cells significantly but 5-FU did not affect beta-catenin levels. Conclusion: The results indicate that niclosamide induces apoptosis and suppresses cell proliferation by inhibiting Wnt/beta-catenin signaling pathway in OVCAR-3 cells. In conclusion, these findings warrant further evaluation of niclosamide as a promising therapy for ovarian cancer.
引用
收藏
页码:178 / 183
页数:6
相关论文
共 30 条
[1]   WNT signalling pathways as therapeutic targets in cancer [J].
Anastas, Jamie N. ;
Moon, Randall T. .
NATURE REVIEWS CANCER, 2013, 13 (01) :11-26
[2]   Inhibition of Wnt/β-catenin pathway by niclosamide: A therapeutic target for ovarian cancer [J].
Arend, Rebecca C. ;
Londono-Joshi, Angelina I. ;
Samant, Rajeev S. ;
Li, Yonghe ;
Conner, Michael ;
Hidalgo, Bertha ;
Alvarez, Ronald D. ;
Landen, Charles N. ;
Straughn, J. Michael ;
Buchsbaum, Donald J. .
GYNECOLOGIC ONCOLOGY, 2014, 134 (01) :112-120
[3]   The Wnt/β-catenin pathway in ovarian cancer: A review [J].
Arend, Rebecca C. ;
Londono-Joshi, Angelina I. ;
Straughn, J. Michael, Jr. ;
Buchsbaum, Donald J. .
GYNECOLOGIC ONCOLOGY, 2013, 131 (03) :772-779
[4]   Diverse mechanisms for activation of Wnt signalling in the ovarian tumour microenvironment [J].
Barbolina, Maria V. ;
Burkhalter, Rebecca J. ;
Stack, M. Sharon .
BIOCHEMICAL JOURNAL, 2011, 437 :1-12
[5]   WNT signaling in ovarian follicle biology and tumorigenesis [J].
Boyer, Alexandre ;
Goff, Alan K. ;
Boerboom, Derek .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2010, 21 (01) :25-32
[6]  
Chang YW, 2006, J FOOD DRUG ANAL, V14, P329
[7]   Anthelminthic drug niclosamide sensitizes the responsiveness of cervical cancer cells to paclitaxel via oxidative stress-mediated mTOR inhibition [J].
Chen, Liping ;
Wang, Li ;
Shen, Haibin ;
Lin, Hui ;
Li, Dan .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2017, 484 (02) :416-421
[8]   The Anti-Helminthic Niclosamide Inhibits Wnt/Frizzled1 Signaling [J].
Chen, Minyong ;
Wang, Jiangbo ;
Lu, Jiuyi ;
Bond, Michael C. ;
Ren, Xiu-Rong ;
Lyerly, H. Kim ;
Barak, Larry S. ;
Chen, Wei .
BIOCHEMISTRY, 2009, 48 (43) :10267-10274
[9]   Inhibition of Wnt signaling by cucurbitacin B in breast cancer cells: Reduction of Wnt-associated proteins and reduced translocation of galectin-3-mediated β-catenin to the nucleus [J].
Dakeng, Sumana ;
Duangmano, Suwit ;
Jiratchariyakul, Weena ;
U-Pratya, Yaowalak ;
Boegler, Oliver ;
Patmasiriwat, Pimpicha .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2012, 113 (01) :49-60
[10]   Preferential Inhibition of Wnt/-Catenin Signaling by Novel Benzimidazole Compounds in Triple-Negative Breast Cancer [J].
Gangrade, Abhishek ;
Pathak, Vibha ;
Augelli-Szafran, Corinne E. ;
Wei, Han-Xun ;
Oliver, Patsy ;
Suto, Mark ;
Buchsbaum, Donald J. .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2018, 19 (05)