Astaxanthin Reduces Stemness Markers in BT20 and T47D Breast Cancer Stem Cells by Inhibiting Expression of Pontin and Mutant p53

被引:20
作者
Ahn, Yong Tae [1 ]
Kim, Min Sung [2 ]
Kim, Youn Sook [3 ]
An, Won Gun [2 ]
机构
[1] Pusan Natl Univ, Res Inst Longev & Well Being, Busan 46241, South Korea
[2] Pusan Natl Univ, Sch Korean Med, Div Pharmacol, Yangsan 50612, South Korea
[3] Pusan Natl Univ, Gene & Cell Therapy Res Ctr Vessel Associated Dis, Yangsan 50612, South Korea
基金
新加坡国家研究基金会;
关键词
astaxanthin; T47D; BT20; pontin; mutp53; cancer stem cells; Oct4; Nanog; siRNA; GAIN-OF-FUNCTION; NANOG; RESISTANCE; PROGNOSIS; PROTEIN; CD44;
D O I
10.3390/md18110577
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Astaxanthin (AST) is a product made from marine organisms that has been used as an anti-cancer supplement. It reduces pontin expression and induces apoptosis in SKBR3, a breast cancer cell line. Using Western blotting and qRT-PCR analyses, this study revealed that in the T47D and BT20 breast cancer cell lines, AST inhibits expression of pontin and mutp53, as well as the Oct4 and Nanog cancer stem cell (CSC) stemness genes. In addition, we explored the mechanism by which AST eradicates breast cancer cells using pontin siRNAs. Pontin knockdown by pontin siRNA reduced proliferation, Oct4 and Nanog expression, colony and spheroid formation, and migration and invasion abilities in breast cancer cells. In addition, reductions in Oct4, Nanog, and mutp53 expression following rottlerin treatment confirmed the role of pontin in these cells. Therefore, pontin may play a central role in the regulation of CSC properties and in cell proliferation following AST treatment. Taken together, these findings demonstrate that AST can repress CSC stemness genes in breast cancer cells, which implies that AST therapy could be used to improve the efficacy of other anti-cancer therapies against breast cancer cells.
引用
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页数:14
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共 45 条
[1]   Isolation, identification, and characterization of cancer stem cells: A review [J].
Abbaszadegan, Mohammad Reza ;
Bagheri, Vahid ;
Razavi, Mahya Shariat ;
Momtazi, Amir Abbas ;
Sahebkar, Amirhossein ;
Gholamin, Mehran .
JOURNAL OF CELLULAR PHYSIOLOGY, 2017, 232 (08) :2008-2018
[2]   p53: The barrier to cancer stem cell formation [J].
Aloni-Grinstein, Ronit ;
Shetzer, Yoav ;
Kaufman, Tom ;
Rotter, Varda .
FEBS LETTERS, 2014, 588 (16) :2580-2589
[3]   Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment [J].
Aponte, Pedro M. ;
Caicedo, Andres .
STEM CELLS INTERNATIONAL, 2017, 2017
[4]   Pontin52, an interacticon partner of β-catenin, binds to the TATA box binding protein [J].
Bauer, A ;
Huber, O ;
Kemler, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14787-14792
[5]   Regulatory networks in embryo-derived pluripotent stem cells [J].
Boiani, M ;
Schöler, HR .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (11) :872-884
[6]   Pontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells [J].
Boo, Kyungjin ;
Bhin, Jinhyuk ;
Jeon, Yoon ;
Kim, Joomyung ;
Shin, Hi-Jai R. ;
Park, Jong-Eun ;
Kim, Kyeongkyu ;
Kim, Chang Rok ;
Jang, Hyonchol ;
Kim, In-Hoo ;
Kim, V. Narry ;
Hwang, Daehee ;
Lee, Ho ;
Baek, Sung Hee .
NATURE COMMUNICATIONS, 2015, 6
[7]   Functional expression cloning of Nanog, a pluripotency sustaining factor in embryonic stem cells [J].
Chambers, I ;
Colby, D ;
Robertson, M ;
Nichols, J ;
Lee, S ;
Tweedie, S ;
Smith, A .
CELL, 2003, 113 (05) :643-655
[8]   Stem cell technology in breast cancer: current status and potential applications [J].
Chiotaki, Rena ;
Polioudaki, Hara ;
Theodoropoulos, Panayiotis A. .
STEM CELLS AND CLONING-ADVANCES AND APPLICATIONS, 2016, 9 :17-29
[9]   A role for cancer stem cells in therapy resistance: Cellular and molecular mechanisms [J].
Cojoc, Monica ;
Maebert, Katrin ;
Muders, Michael H. ;
Dubrovska, Anna .
SEMINARS IN CANCER BIOLOGY, 2015, 31 :16-27
[10]   CD24 Expression and differential resistance to chemotherapy in triple-negative breast cancer [J].
Deng, Xinyu ;
Apple, Sophia ;
Zhao, Hong ;
Song, Jeongyoon ;
Lee, Minna ;
Luo, William ;
Wu, Xiancheng ;
Chung, Debra ;
Pietras, Richard J. ;
Chang, Helena R. .
ONCOTARGET, 2017, 8 (24) :38294-38308