Telomerase Inhibitor TMPyP4 Alters Adhesion and Migration of Breast-Cancer Cells MCF7 and MDA-MB-231

被引:35
作者
Konieczna, Natalia [1 ,2 ]
Romaniuk-Drapala, Aleksandra [1 ]
Lisiak, Natalia [1 ]
Toton, Ewa [1 ]
Paszel-Jaworska, Anna [1 ]
Kaczmarek, Mariusz [3 ]
Rubis, Blazej [1 ]
机构
[1] Poznan Univ Med Sci, Dept Clin Chem & Mol Diagnost, 49 Przybyszewskiego St, PL-60355 Poznan, Poland
[2] Dept Med Diagnost, 38A Dobra St, PL-60595 Poznan, Poland
[3] Poznan Univ Med Sci, Chair Clin Immunol, Dept Immunol, 5D Rokietnicka St, PL-60806 Poznan, Poland
关键词
TMPyP4; telomerase; hTERT; adhesion; migration; cell cycle; breast cancer; MCF7; MDA-MB-231; MCF-12A; DNA-DAMAGE RESPONSE; C-MYC; PROLIFERATION; EXPRESSION; ARREST; TERT;
D O I
10.3390/ijms20112670
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human telomeres were one of the first discovered and characterized sequences forming quadruplex structures. Association of these structures with oncogenic and tumor suppressor proteins suggests their important role in cancer development and therapy efficacy. Since cationic porphyrin TMPyP4 is known as G-quadruplex stabilizer and telomerase inhibitor, the aim of the study was to analyze the anticancer properties of this compound in two different human breast-cancer MCF7 and MDA-MB-231 cell lines. The cytotoxicity of TMPyP4 alone or in combination with doxorubicin was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromid) and clonogenic assays, and the cell-cycle alterations were analyzed by flow cytometry. Telomerase expression and activity were evaluated using qPCR and telomeric repeat amplification protocol (TRAP) assays, respectively. The contribution of G-quadruplex inhibitor to protein pathways engaged in cell survival, DNA repair, adhesion, and migration was performed using immunodetection. Scratch assay and functional assessment of migration and cell adhesion were also performed. Consequently, it was revealed that in the short term, TMPyP4 neither revealed cytotoxic effect nor sensitized MCF7 and MDA-MB-231 to doxorubicin, but altered breast-cancer cell adhesion and migration. It suggests that TMPyP4 might substantially contribute to a significant decrease in cancer cell dissemination and, consequently, cancer cell survival reduction. Importantly, this effect might not be associated with telomeres or telomerase.
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页数:20
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共 42 条
[1]   Cell Proliferation and Cytotoxicity Assays [J].
Adan, Aysun ;
Kiraz, Yagmur ;
Baran, Yusuf .
CURRENT PHARMACEUTICAL BIOTECHNOLOGY, 2016, 17 (14) :1213-1221
[2]   Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? [J].
Balasubramanian, Shankar ;
Hurley, Laurence H. ;
Neidle, Stephen .
NATURE REVIEWS DRUG DISCOVERY, 2011, 10 (04) :261-275
[3]   Differential effects of doxorubicin treatment on cell cycle arrest and Skp2 expression in breast cancer cells [J].
Bar-On, Ortal ;
Shapira, Ma'anit ;
Hershko, Dan D. .
ANTI-CANCER DRUGS, 2007, 18 (10) :1113-1121
[4]  
Brooks Tracy A, 2010, Genes Cancer, V1, P641
[5]   TMPYP4 exerted antitumor effects in human cervical cancer cells through activation of p38 mitogen-activated protein kinase [J].
Cheng, Ming-Jun ;
Cao, Yun-Gui .
BIOLOGICAL RESEARCH, 2017, 50
[6]   TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program [J].
Choi, Jinkuk ;
Southworth, Lucinda K. ;
Sarin, Kavita Y. ;
Venteicher, Andrew S. ;
Ma, Wenxiu ;
Chang, Woody ;
Cheung, Peggie ;
Jun, Sohee ;
Artandi, Maja K. ;
Shah, Naman ;
Kim, Stuart K. ;
Artandi, Steven E. .
PLOS GENETICS, 2008, 4 (01) :0124-0138
[7]   The cancer cell adhesion resistome: mechanisms, targeting and translational approaches [J].
Dickreuter, Ellen ;
Cordes, Nils .
BIOLOGICAL CHEMISTRY, 2017, 398 (07) :721-735
[8]  
Duensing Thomas D, 2018, Cold Spring Harb Protoc, V2018, DOI 10.1101/pdb.prot093807
[9]   Clonogenic assay of cells in vitro [J].
Franken, Nicolaas A. P. ;
Rodermond, Hans M. ;
Stap, Jan ;
Haveman, Jaap ;
van Bree, Chris .
NATURE PROTOCOLS, 2006, 1 (05) :2315-2319
[10]   Antitumor Effects of Telomerase Inhibitor TMPyP4 in Osteosarcoma Cell Lines [J].
Fujimori, Jun ;
Matsuo, Toshihiro ;
Shimose, Shoji ;
Kubo, Tadahiko ;
Ishikawa, Masakazu ;
Yasunaga, Yuji ;
Ochi, Mitsuo .
JOURNAL OF ORTHOPAEDIC RESEARCH, 2011, 29 (11) :1707-1711