Effect of topotycan and zinc oxide nanoparticles combination on cytotoxicity and P53 gene expression against breast cancer (MCF-7) cell line

authors:

avatar Alireza Sharifian , avatar fahimeh baghbani , * , avatar Hasan Sahebjami


how to cite: Sharifian A, baghbani F, Sahebjami H. Effect of topotycan and zinc oxide nanoparticles combination on cytotoxicity and P53 gene expression against breast cancer (MCF-7) cell line. koomesh. 2020;22(1):e153167. 

Abstract

Introduction: Breast cancer is one of the most common malignancies in women worldwide. Today, nanoparticles are one of the hopes of treatment and diagnosis of many diseases, including cancer. the The present study aimed to explore the effect of topotycan and zinc oxide nanoparticles (ZnONPs) combination on cytotoxicity and P53 gene expression in MCF7 breast cancer cells. Materials and Methods: Cancerous MCF7 cell line were treated with different concentrations of ZnONPs and topotecan as an anti-cancer drug, separately, as well as combined formulation. Then, the cell viability was evaluated using MTT assay. The expression level of P53 gene was evaluated in treated cells via real time PCR after RNA extraction and cDNA synthesis. Results: According to MTT results, the ZnONPs and topotecan significantly decreased the viability of MCF7 cells in a dose-dependent manner. Also, the combined effect of ZnONPS and topotecan on the MCF7 cell line at concentrations of 45 mol/ml of zinc and different concentrations of topotecan had an additional toxic effect. Our data revealed that mRNA level of P53 was up regulated (1.3-fold) in cells treated with topotecan combined with ZnONPs. Conclusion: Our results demonstrated that combination of the topotecan and ZnONPs could have a powerful synergistic cytotoxic effect on breast cancer cell line.

References

  • 1.

    DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin 2014; 64: 52-62.

  • 2.

    Hollstein M, Sidransky D, Vogelstein B, Harris CC. P53 mutations in human cancers. Science 1991; 253: 49-53.

  • 3.

    Menendez JA, Lupu R. RNA interference-mediated silencing of the p53 tumor-suppressor protein drastically increases apoptosis after inhibition of endogenous fatty acid metabolism in breast cancer cells. Int J Mol Med 2005; 15: 33-40.

  • 4.

    Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323-331.

  • 5.

    Lane DP, Lu X, Hupp T, Hall PA. The role of the p53 protein in the apoptotic response. Philos Trans R Soc Lond B Biol Sci 1994; 345: 277-280.

  • 6.

    Mashimo T, Watabe M, Hirota S, Hosobe S, Miura K, Tegtmeyer PJ, et al. The expression of the KAI1 gene, a tumor metastasis suppressor, is directly activated by p53. Proc Natl Acad Sci USA 1998; 95: 11307-11311.

  • 7.

    Zou Z, Gao C, Nagaich AK, Connell T, Saito S, Moul JW et al. p53 regulates the expression of the tumor suppressor gene maspin. J Biol Chem 2000; 275: 6051-6054.

  • 8.

    Hulla J, Sahu S, Hayes A. Nanotechnology: History and future. Hum Exp Toxicol 2015; 34: 1318-1321.

  • 9.

    Souza LG, Silva EJ, Martins AL, Mota MF, Braga RC, Lima EM, et al. Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release. Eur J Pharm Biopharm 2011; 79: 189-196.

  • 10.

    Shen B, Zhao K, Ma S, Yuan D, Bai Y. Topotecan-loaded mesoporous silica nanoparticles for reversing multi-drug resistance by synergetic chemoradiotherapy. Chem Asian J 2015; 10: 344-348.

  • 11.

    Nguyen D, Zajac-Kaye M, Rubinstein L, Voeller D, Tomaszewski JE, Kummar S, et al. Poly(ADP-ribose) polymerase inhibition enhances p53-dependent and independent DNA damageresponses induced by DNA damaging agent. Cell Cycle 2011; 10: 4074-4082.

  • 12.

    Patankar NA, Waterhouse D, Strutt D, Anantha M, Bally MB. topophore C: a liposomal nanoparticle formulation of topotecan for treatment of ovarian cancer. Invest New Drugs 2013; 31: 46-58.

  • 13.

    Mira K, Kwangsu O, Keunchang Ch, Sang-Woo J, So YL. Live-cell monitoring of the glutathione-triggered release of the anticancer drug topotecan on gold nanoparticles in serum-containing media. Chem Commun 2012; 48: 4205-4207.

  • 14.

    Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H. Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med 2014; 5: 927-946.

  • 15.

    Shandiz SA, Farasati S, Saeedi B, Baghbani-Arani F, Akbari Asl E, Keshavarz-Pakseresht B, et al. Up regulation of KAI1 gene expression and apoptosis effect of imatinib mesylate in gastric adenocarcinoma (AGS) cell line. Asian Pac J Trop Dis 2016; 6: 120-125.

  • 16.

    Santini D, Stumbo L, Spoto C, D'Onofrio L, Pantano F, Iuliani M, et al. Bisphosphonates as anticancer agents in early breast cancer: preclinical and clinical evidence. Breast Cancer Res 2015; 17: 121.

  • 17.

    Wahab R, Dwivedi S, Umar A, Singh S, Hwang IH, Shin HS, et al. ZnO nanoparticles induce oxidative stress in Cloudman S91 melanoma cancer cells. J Biomed Nanotechnol 2013; 9: 441-449.##.