Reversine, a Substituted Purine, Exerts an Inhibitive Effect on Human Renal Carcinoma Cells Via Induction of Cell Apoptosis and Polyploidy

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2018 Mar 10

PMID 29520153

Citations 11

Authors

Li Cheng

Hao Wang

Kecun Guo

Zicheng Wang

Zhongyuan Zhang

Cheng Shen

Liang Chen

Jian Lin

Affiliations

Soon will be listed here.

Abstract

Background: Human renal cell carcinoma (RCC) is the most common type of kidney cancer that arises from the renal epithelium. Up to 33.3% of RCC patients treated with local tumor resections will subsequently develop recurrence or metastases. Thus, optimized therapeutic regimes are urgently needed to improve the prognosis of RCC. Reversine was recently reported to exert critical roles in cancer therapy.

Materials And Methods: This study evaluated the anti-tumor effects of reversine on cell viability, colony formation, apoptosis, and cell cycle in 786-O and ACHN cell lines.

Results: It was demonstrated that reversine significantly inhibited the proliferation of both cell lines in time- and dose-dependent manners. Polyploidy formation was observed under high-concentration reversine treatment. In addition, reversine induced cell death via caspase-dependent apoptotic pathways, which could be partially inhibited by Z-VAD-FMK, a pan-caspase inhibitor.

Conclusion: Reversine could effectively suppress the proliferation of human RCC cells, and may serve as a novel therapeutic regimen for RCC in clinical practice.

Citing Articles

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References

Kurozumi A, Kato M, Goto Y, Matsushita R, Nishikawa R, Okato A . Regulation of the collagen cross-linking enzymes LOXL2 and PLOD2 by tumor-suppressive microRNA-26a/b in renal cell carcinoma. Int J Oncol. 2016; 48(5):1837-46. PMC: 4809659. DOI: 10.3892/ijo.2016.3440. View

Lindqvist A, van Zon W, Rosenthal C, Wolthuis R . Cyclin B1-Cdk1 activation continues after centrosome separation to control mitotic progression. PLoS Biol. 2007; 5(5):e123. PMC: 1858714. DOI: 10.1371/journal.pbio.0050123. View

Perreira M, Jiang J, Klutz A, Gao Z, Shainberg A, Lu C . "Reversine" and its 2-substituted adenine derivatives as potent and selective A3 adenosine receptor antagonists. J Med Chem. 2005; 48(15):4910-8. PMC: 3474371. DOI: 10.1021/jm050221l. View

Ljungberg B, Bensalah K, Canfield S, Dabestani S, Hofmann F, Hora M . EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol. 2015; 67(5):913-24. DOI: 10.1016/j.eururo.2015.01.005. View

Cohen H, McGovern F . Renal-cell carcinoma. N Engl J Med. 2005; 353(23):2477-90. DOI: 10.1056/NEJMra043172. View

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh J, Comber H . Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013; 49(6):1374-403. DOI: 10.1016/j.ejca.2012.12.027. View

Motzer R, Bander N, Nanus D . Renal-cell carcinoma. N Engl J Med. 1996; 335(12):865-75. DOI: 10.1056/NEJM199609193351207. View

Znaor A, Lortet-Tieulent J, Laversanne M, Jemal A, Bray F . International variations and trends in renal cell carcinoma incidence and mortality. Eur Urol. 2014; 67(3):519-30. DOI: 10.1016/j.eururo.2014.10.002. View

McMillin D, Delmore J, Weisberg E, Negri J, Geer D, Klippel S . Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med. 2010; 16(4):483-9. PMC: 3786785. DOI: 10.1038/nm.2112. View

10.

Kuo C, Lu Y, Tseng Y, Shi C, Chen S, Chen P . Reversine induces cell cycle arrest, polyploidy, and apoptosis in human breast cancer cells. Breast Cancer. 2012; 21(3):358-69. DOI: 10.1007/s12282-012-0400-z. View

11.

Soung Y, Lee J, Kim S, Sung Y, Park W, Nam S . Caspase-8 gene is frequently inactivated by the frameshift somatic mutation 1225_1226delTG in hepatocellular carcinomas. Oncogene. 2004; 24(1):141-7. DOI: 10.1038/sj.onc.1208244. View

12.

Anastasia L, Sampaolesi M, Papini N, Oleari D, Lamorte G, Tringali C . Reversine-treated fibroblasts acquire myogenic competence in vitro and in regenerating skeletal muscle. Cell Death Differ. 2006; 13(12):2042-51. DOI: 10.1038/sj.cdd.4401958. View

13.

Nigg E . Mitotic kinases as regulators of cell division and its checkpoints. Nat Rev Mol Cell Biol. 2001; 2(1):21-32. DOI: 10.1038/35048096. View

14.

Hsieh T, Traganos F, Darzynkiewicz Z, Wu J . The 2,6-disubstituted purine reversine induces growth arrest and polyploidy in human cancer cells. Int J Oncol. 2007; 31(6):1293-300. PMC: 2582159. View

15.

Jung D, Williams D . Novel chemically defined approach to produce multipotent cells from terminally differentiated tissue syncytia. ACS Chem Biol. 2011; 6(6):553-62. DOI: 10.1021/cb2000154. View

16.

Harrington E, Bebbington D, Moore J, Rasmussen R, Ajose-Adeogun A, Nakayama T . VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med. 2004; 10(3):262-7. DOI: 10.1038/nm1003. View

17.

Lanzi C, Cassinelli G, Cuccuru G, Supino R, Zuco V, Ferlini C . Cell cycle checkpoint efficiency and cellular response to paclitaxel in prostate cancer cells. Prostate. 2001; 48(4):254-64. DOI: 10.1002/pros.1105. View

18.

Lee Y, Wu W, Ji W, Chen J, Cheng Y, Chiang M . Reversine suppresses oral squamous cell carcinoma via cell cycle arrest and concomitantly apoptosis and autophagy. J Biomed Sci. 2012; 19:9. PMC: 3299600. DOI: 10.1186/1423-0127-19-9. View

19.

Hua S, Chang T, Chen H, Lu C, Liu Y, Chen S . Reversine, a 2,6-disubstituted purine, as an anti-cancer agent in differentiated and undifferentiated thyroid cancer cells. Pharm Res. 2012; 29(7):1990-2005. DOI: 10.1007/s11095-012-0727-3. View

20.

Soussi T, Lozano G . p53 mutation heterogeneity in cancer. Biochem Biophys Res Commun. 2005; 331(3):834-42. DOI: 10.1016/j.bbrc.2005.03.190. View