Anticancer activity of a trans-platinum(II) complex of 3-aminoflavone to ovarian cancer cells
Abstract
Objectives: Cisplatin is a classical anticancer drug used in the treatment of ovarian cancer. Unfortunately, the treatment is associated with numerous adverse effects. Studies concerning new platinum derivatives with less organ toxicity are conducted. The aim of this study was to analyse the effect of a new trans-platinum(II) complex of 3-aminoflavone on the viability and mortality of the cells from OVCAR 3 and CAOV 3 ovarian cancer cell lines and on the expression of the selected genes involved in the process of apoptosis.
Material and methods: The viability of ovarian cancer cells and the cytotoxicity of a trans-platinum(II) complex of 3-aminoflavone: [trans-Pt(3-af )2Cl2), trans-bis-(3-aminoflavone) dichloridoplatinum(II)] and cisplatin were analysed using a spectrophotometric method with the use of MTT assay and LDH assay. BAX, BCL2, BIRC5 gene expression analysis on mRNA level was conducted with the use of Real-Time PCR method.
Results: It was observed that parallel to an increase in the concentration of the new complex compound and cisplatin there is a decrease in viability and an increase in mortality of ovarian cancer cells. As a result of exposure to the studied compound and cisplatin, an increased BAX gene expression and decreased BCL2 and BIRC5 gene expression were observed in the studied ovarian cancer cell lines.
Conclusion: Trans-Pt(3-af )2Cl2 exhibits anticancer activity towards OVCAR 3 and CAOV 3 ovarian cancer cell lines. The studied complex compound can be considered as a potential anticancer drug.
Keywords: Trans-Pt(3-af )2Cl2cisplatinovarian cancerOVCAR 3CAOV 3viabilityapoptosis
References
- ROSENBERG B, VANCAMP L, KRIGAS T. INHIBITION OF CELL DIVISION IN ESCHERICHIA COLI BY ELECTROLYSIS PRODUCTS FROM A PLATINUM ELECTRODE. Nature. 1965; 205: 698–699.
- Pinto AL, Lippard SJ. Binding of the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin) to DNA. Biochim Biophys Acta. 1985; 780(3): 167–180.
- Gonzalez VM, Fuertes MA, Alonso C, et al. Is cisplatin-induced cell death always produced by apoptosis? Mol Pharmacol. 2001; 59(4): 657–663.
- Helm CW, States JC. Enhancing the efficacy of cisplatin in ovarian cancer treatment - could arsenic have a role. J Ovarian Res. 2009; 2: 2.
- Subocz M, Popławska B, Bielawska A, et al. Pochodne platyny w chemioterapii chorób nowotworowych. Ann. Acad. Med. Siles. 2011, 65. ; 4: 70–76.
- Dudziak J, Słomczyński M, Torliński L. Powikłania kardiologiczne po chemioterapii— patomechanizm, diagnostyka, leczenie i zapobieganie . Choroby Serca i Naczyń. 2009, 6. ; 2: 73–81.
- Johnson N, Butour JL, Villani G, et al. Metal Antitumor Compounds: The Mechanism of Action of Platinum Complexes. Progress in Clinical Biochemistry and Medicine. 1989: 1–24.
- Fanelli M, Formica M, Fusi V, et al. New trends in platinum and palladium complexes as antineoplastic agents. Coordination Chemistry Reviews. 2016; 310: 41–79.
- Trynda-Lemiesz L, Śliwińska-Hill U. Kompleksy metali w terapii nowotworowej. Teraźniejszość i przyszłość NOWOTWORY Journal of Oncology. 2011, 61. ; 5: 465–474.
- Aris SM, Farrell NP. Towards Antitumor Active trans-Platinum Compounds. Eur J Inorg Chem. 2009; 2009(10): 1293.
- Fabijańska M, Studzian K, Szmigiero L, et al. trans-Platinum(II) complex of 3-aminoflavone - synthesis, X-ray crystal structure and biological activities in vitro. Dalton Trans. 2015; 44(3): 938–947.
- Matlawska-Wasowska K, Rainczuk K, Kalinowska-Lis U, et al. Genotoxicity of novel trans-platinum(II) complex with diethyl (pyridin-4-ylmethyl)phosphate in human non-small cell lung cancer cells A549. Chem Biol Interact. 2007; 168(2): 135–142.
- Herrera JM, Mendes F, Gama S, et al. Design and biological evaluation of new platinum(II) complexes bearing ligands with DNA-targeting ability. Inorg Chem. 2014; 53(23): 12627–12634.
- Krajowa Baza Danych Nowotworowych – Zakład Epidemiologii i Prewencji Nowotworów Centrum Onkologii. : Warszawa.
- http://globocan.iarc.fr/Default.aspx..
- Nowak-Markwitz E, Spaczyński M. Ovarian cancer--modern approach to its origin and histogenesis. Ginekol Pol. 2012; 83(6): 454–457.
- Lengyel E. Ovarian cancer development and metastasis. Am J Pathol. 2010; 177(3): 1053–1064.
- Desjardins M, Xie J, Gurler H, et al. Versican regulates metastasis of epithelial ovarian carcinoma cells and spheroids. J Ovarian Res. 2014; 7: 70.
- Dubeau L. The cell of origin of ovarian epithelial tumors and the ovarian surface epithelium dogma: does the emperor have no clothes? Gynecol Oncol. 1999; 72(3): 437–442.
- Kujawa KA, Lisowska KM. Ovarian cancer--from biology to clinic. Postepy Hig Med Dosw (Online). 2015; 69: 1275–1290.
- Brigulová K, Cervinka M, Tošner J, et al. Chemoresistance testing of human ovarian cancer cells and its in vitro model. Toxicol In Vitro. 2010; 24(8): 2108–2115.
- de Bree E, Theodoropoulos PA, Rosing H, et al. Treatment of ovarian cancer using intraperitoneal chemotherapy with taxanes: from laboratory bench to bedside. Cancer Treat Rev. 2006; 32(6): 471–482.
- Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144(5): 646–674.
- Szala S. Swoista indukcja apoptozy w komórkach nowotworowych. NOWOTWORY. 2000, 50. ; 2: 111–121.
- Rzońca S, Małecki M. Proapoptotyczna terapia genowa a wrażliwość nowotworów na chemioterapię. Współczesna Onkol. 2009; 13: 61–65.
- Ealovega MW, McGinnis PK, Sumantran VN, et al. bcl-xs gene therapy induces apoptosis of human mammary tumors in nude mice. Cancer Res. 1996; 56(9): 1965–1969.
- Holcik M. The IAP proteins. Trends in Genetics. 2002; 18(10): 537–538.
- www.mskcc.org/research-advantage/support/technology/tangible-material/caov-3-human-ovarian-cell-line.
- Kloudová K, Hromádková H, Partlová S, et al. Expression of tumor antigens on primary ovarian cancer cells compared to established ovarian cancer cell lines. Oncotarget. 2016; 7(29): 46120–46126.
- Gibb RK, Taylor DD, Wan T, et al. Apoptosis as a measure of chemosensitivity to cisplatin and taxol therapy in ovarian cancer cell lines. Gynecol Oncol. 1997; 65(1): 13–22.
- Hamilton TC, Young RC, McKoy WM, et al. Characterization of a human ovarian carcinoma cell line (NIH:OVCAR-3) with androgen and estrogen receptors. Cancer Res. 1983; 43(11): 5379–5389.
- Wcisło G. High-dose chemotherapy of ovarian cancer followed by bone marrow transplantation or peripheral blood stem cell support. Współczesna Onkol. 2005, 9. ; 1: 14–22.
- van Haaften C, Boot A, Corver WE, et al. Synergistic effects of the sesquiterpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells. J Exp Clin Cancer Res. 2015: 34–38.
- Pommier Y, Sordet O, Antony S, et al. Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene. 2004; 23(16): 2934–2949.
- Natile G, Coluccia M. Current status of trans-platinum compounds in cancer therapy. Coordination Chemistry Reviews. 2001; 216-217: 383–410.
- Smith JA, Ngo H, Martin MC, et al. An evaluation of cytotoxicity of the taxane and platinum agents combination treatment in a panel of human ovarian carcinoma cell lines. Gynecol Oncol. 2005; 98(1): 141–145.
- Thomadaki H, Scorilas A. Molecular profile of breast versus ovarian cancer cells in response to treatment with the anticancer drugs cisplatin, carboplatin, doxorubicin, etoposide and taxol. Biol Chem. 2008; 389(11): 1427–1434.
- Ding L, Wang XQ, Zhang J, et al. Underlying mechanism of 2-methoxyestradiol-induced apoptosis and growth arrest in SKOV3 human ovarian cancer cells. Eur Rev Med Pharmacol Sci. 2015; 19(11): 2084–2090.
- Kosmider B, Wojcik I, Osiecka R, et al. Enhanced P53 and BAX gene expression and apoptosis in A549 cells by cis-Pt(II) complex of 3-aminoflavone in comparison with cis-DDP. Invest New Drugs. 2005; 23(4): 287–297.
- Lesan V, Ghaffari SH, Salaramoli J, et al. Evaluation of antagonistic effects of metformin with Cisplatin in gastric cancer cells. Int J Hematol Oncol Stem Cell Res. 2014; 8(3): 12–19.
- Wang Z, Xie Y, Wang H. Changes in survivin messenger RNA level during chemotherapy treatment in ovarian cancer cells. Cancer Biology & Therapy. 2014; 4(7): 716–719.
