Anticancer Activity of Some Ruthenium(III) Complexes with Quinolone Antibiotics: In Vitro Cytotoxicity, Cell Cycle Modulation, and Apoptosis-Inducing Properties in LoVo Colon Cancer Cell Line

被引:13
作者
Mihaila, Mirela [1 ]
Hotnog, Camelia Mia [1 ]
Bostan, Marinela [1 ]
Munteanu, Alexandra Cristina [2 ]
Vacaroiu, Ileana Adela [3 ]
Brasoveanu, Lorelei Irina [1 ]
Uivarosi, Valentina [2 ]
机构
[1] Romanian Acad, Stefan S Nicolau Inst Virol, Ctr Immunol, 285 Mihai Bravu Ave, Bucharest 030304, Romania
[2] Carol Davila Univ Med & Pharm, Fac Pharm, Dept Gen & Inorgan Chem, 6 Traian Vuia St, Bucharest 020956, Romania
[3] Carol Davila Univ Med & Pharm, Fac Med, Dept Nephrol, 8 Eroii Sanitari Ave, Bucharest 050474, Romania
来源
APPLIED SCIENCES-BASEL | 2021年 / 11卷 / 18期
关键词
ruthenium complexes; quinolones; cancer drug resistance; colon cancer; cytotoxicity; apoptosis; cell cycle; DRUG-RESISTANCE; LIPID NANOCARRIERS; III COMPLEXES; NAMI-A; PT(IV); TOPOISOMERASES; MACHINERY; CISPLATIN; VOSAROXIN; THERAPY;
D O I
10.3390/app11188594
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Cisplatin is one of the most effective anticancer agents used to treat colon cancer, which is the third malignancy between the most common human cancers in the world, but the resistance developed represents an obstacle against the full success of chemotherapy. An emerging interest appeared in finding other metallic compounds, such as ruthenium(III) complexes, for chemotherapeutic application in cancer. Our study focused on the anticancer activity of several ruthenium (Ru) complexes with quinolone antibiotics in colon tumor cell cultures. Real-time cell analysis and drug-mediated cytotoxicity tests monitored the inhibitory effects in the drug-treated LoVo colon cancer cells. Flow cytometry assays were performed to evaluate cell cycle phases distribution and apoptotic events. The obtained results showed dose-dependent increased levels of cell lysis and induction of apoptosis in LoVo cancer cells treated with the Ru(III) complexes. In addition, data showed a major decrease in cell proliferation, since the percentages of cells distributed in the S cell cycle phase diminished, and a G0/G1 cell arrest was observed. Therefore, our results strongly suggest that the newly synthesized Ru(III) complexes might play an important role in future chemotherapeutic approaches, since their activity is based on diminishing cell proliferation, induction of apoptosis, and modulation of cell cycle phases.
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页数:19
相关论文
共 73 条
[1]   Ligand substitutions between ruthenium-cymene compounds can control protein versus DNA targeting and anticancer activity [J].
Adhireksan, Zenita ;
Davey, Gabriela E. ;
Campomanes, Pablo ;
Groessl, Michael ;
Clavel, Catherine M. ;
Yu, Haojie ;
Nazarov, Alexey A. ;
Yeo, Charmian Hui Fang ;
Ang, Wee Han ;
Droege, Peter ;
Rothlisberger, Ursula ;
Dyson, Paul J. ;
Davey, Curt A. .
NATURE COMMUNICATIONS, 2014, 5
[2]   Voreloxin, a First-in-Class Anticancer Quinolone Derivative, in Relapsed/Refractory Solid Tumors: A Report on Two Dosing Schedules [J].
Advani, Ranjana H. ;
Hurwitz, Herbert I. ;
Gordon, Michael S. ;
Ebbinghaus, Scot W. ;
Mendelson, David S. ;
Wakelee, Heather A. ;
Hoch, Ute ;
Silverman, Jeffrey A. ;
Havrilla, Nancy A. ;
Berman, Craig J. ;
Fox, Judith A. ;
Allen, Roberta S. ;
Adelman, Daniel C. .
CLINICAL CANCER RESEARCH, 2010, 16 (07) :2167-2175
[3]  
Ahmed A, 2012, J PHARM PHARM SCI, V15, P52
[4]   Structural and chelation behaviors of new Ru(II), Pt(IV) and Ir(III) gatifloxacin drug complexes: Spectroscopic characterizations [J].
Alghamdi, Mohammed T. ;
Alsibaai, A. A. ;
El-Shahawi, M. S. ;
Refat, Moamen S. .
JOURNAL OF MOLECULAR STRUCTURE, 2017, 1130 :264-275
[5]   Synthesis and spectroscopic studies of levofloxacin uni-dentate complexes of Ru(II), Pt(IV) and Ir(III): Third generation of quinolone antibiotic drug complexes [J].
Alghamdi, Mohammed T. ;
Alsibaai, A. A. ;
Shahawi, M. S. ;
Refat, Moamen S. .
JOURNAL OF MOLECULAR LIQUIDS, 2016, 224 :571-579
[6]   Synthesis, spectroscopic, thermal, antimicrobial and electrochemical characterization of some novel Ru(iii), Pt(iv) and Ir(iii) complexes of pipemidic acid [J].
Alibrahim, Khuloud A. ;
Al-Saif, Foziah A. ;
Alghamdi, M. T. ;
El-Shahawi, M. S. ;
Moustafa, Y. M. ;
Refat, Moamen S. .
RSC ADVANCES, 2018, 8 (40) :22515-22529
[7]   Type II topoisomerases as targets for quinolone antibacterials: turning Dr. Jekyll into Mr. Hyde [J].
Anderson, VE ;
Osheroff, N .
CURRENT PHARMACEUTICAL DESIGN, 2001, 7 (05) :337-353
[8]  
[Anonymous], 2018, CA Cancer J Clin, DOI DOI 10.3322/caac.20115
[9]  
Arsene A. L., 2011, Biopolymers and Cell, V27, P141
[10]  
Arsene AL, 2016, FARMACIA, V64, P712