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Apoptotic effects of salinomycin on human ovarian cancer cell line (OVCAR-3)

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Tumor Biology

Abstract

In this study, we studied the apoptotic and cytotoxic effects of salinomycin on human ovarian cancer cell line (OVCAR-3) as salinomycin is known as a selectively cancer stem cell killer agent. We used immortal human ovarian epithelial cell line (IHOEC) as control group. Ovarian cancer cells and ovarian epithelial cells were treated by different concentrations of salinomycin such as 0.1, 1, and 40 μM and incubated for 24, 48, and 72 h. Dimethylthiazol (MTT) cell viability assay was performed to determine cell viability and toxicity. On the other hand, the expression levels of some of the apoptosis-related genes, namely anti-apoptotic Bcl-2, apoptotic Bax, and Caspase-3 were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, Caspase-3 protein level was also determined. As a result, we concluded that incubation of human OVCAR-3 by 0.1 μM concentration of salinomycin for 24 h killed 40 % of the cancer cells by activating apoptosis but had no effect on normal cells. The apoptotic Bax gene expression was upregulated but anti-apoptotic Bcl-2 gene expression was downregulated. Active Caspase-3 protein level was increased significantly (p < 0.05).

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References

  1. Jemal A et al. Cancer statistics, 2006. CA Cancer J Clin. 2006;56(2):106–30.

    Article  PubMed  Google Scholar 

  2. Aletti GD et al. Current management strategies for ovarian cancer. Mayo Clin Proc. 2007;82(6):751–70.

    Article  PubMed  Google Scholar 

  3. Eum KH, Lee M. Crosstalk between autophagy and apoptosis in the regulation of paclitaxel-induced cell death in v-Ha-ras-transformed fibroblasts. Mol Cell Biochem. 2011;348(1–2):61–8.

    Article  CAS  PubMed  Google Scholar 

  4. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26(4):239–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Engel T, Henshall DC. Apoptosis, Bcl-2 family proteins and caspases: the ABCs of seizure-damage and epileptogenesis? Int J Physiol Pathophysiol Pharmacol. 2009;1(2):97–115.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Ghobrial IM, Witzig TE, Adjei AA. Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin. 2005;55(3):178–94.

    Article  PubMed  Google Scholar 

  7. Tsujimoto Y. Role of Bcl-2 family proteins in apoptosis: apoptosomes or mitochondria? Genes Cells. 1998;3(11):697–707.

    Article  CAS  PubMed  Google Scholar 

  8. Miyazaki Y et al. Salinomycin, a new polyether antibiotic. J Antibiot. 1974;27(11):814–21.

    Article  CAS  PubMed  Google Scholar 

  9. Mitani M, Yamanishi T, Miyazaki Y. Salinomycin: a new monovalent cation ionophore. Biochem Biophys Res Commun. 1975;66(4):1231–6.

    Article  CAS  PubMed  Google Scholar 

  10. Butaye P, Devriese LA, Haesebrouck F. Antimicrobial growth promoters used in animal feed: effects of less well known antibiotics on gram-positive bacteria. Clin Microbiol Rev. 2003;16(2):175–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Callaway TR et al. Ionophores: their use as ruminant growth promotants and impact on food safety. Curr Issues Intest Microbiol. 2003;4(2):43–51.

    CAS  PubMed  Google Scholar 

  12. Danforth HD et al. Anticoccidial activity of salinomycin in battery raised broiler chickens. Poult Sci. 1977;56(3):926–32.

    Article  CAS  PubMed  Google Scholar 

  13. Gupta PB et al. Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell. 2009;138(4):645–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bortner CD, Hughes Jr FM, Cidlowski JA. A primary role for K+ and Na+ efflux in the activation of apoptosis. J Biol Chem. 1997;272(51):32436–42.

    Article  CAS  PubMed  Google Scholar 

  15. Fuchs D et al. Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells. Biochem Biophys Res Commun. 2010;394(4):1098–104.

    Article  CAS  PubMed  Google Scholar 

  16. Fuchs D et al. Salinomycin induces apoptosis and overcomes apoptosis resistance in human cancer cells. Biochem Biophys Res Commun. 2009;390(3):743–9.

    Article  CAS  PubMed  Google Scholar 

  17. Morgan DM. Tetrazolium (MTT) assay for cellular viability and activity. Methods Mol Biol. 1998;79:179–83.

    CAS  PubMed  Google Scholar 

  18. Abu-Qare AW, Abou-Donia MB. Biomarkers of apoptosis: release of cytochrome c, activation of caspase-3, induction of 8-hydroxy-2′-deoxyguanosine, increased 3-nitrotyrosine, and alteration of p53 gene. J Toxicol Environ Health B Crit Rev. 2001;4(3):313–32.

    Article  CAS  PubMed  Google Scholar 

  19. Park IS, Kim JE. Potassium efflux during apoptosis. J Biochem Mol Biol. 2002;35(1):41–6.

    CAS  PubMed  Google Scholar 

  20. Parajuli B et al. Salinomycin inhibits Akt/NF-kappaB and induces apoptosis in cisplatin resistant ovarian cancer cells. Cancer Epidemiol. 2013;37(4):512–7.

    Article  CAS  PubMed  Google Scholar 

  21. Kim KY et al. Salinomycin-induced apoptosis of human prostate cancer cells due to accumulated reactive oxygen species and mitochondrial membrane depolarization. Biochem Biophys Res Commun. 2011;413(1):80–6.

    Article  CAS  PubMed  Google Scholar 

  22. Ketola K et al. Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress. Br J Cancer. 2012;106(1):99–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhou J et al. Salinomycin induces apoptosis in cisplatin-resistant colorectal cancer cells by accumulation of reactive oxygen species. Toxicol Lett. 2013;222(2):139–45.

    Article  CAS  PubMed  Google Scholar 

  24. Xu S-q, Z A-z, Liu C-c, Xu T-t, Chen X-y, Liu G-x. Salinomycin inhibits proliferation and induces apoptosis of Gleevec-resistant chronic myeloid leukemic cell line K562/Glv. Chin J Pathophysiol. 2012;28:1208–1212.

  25. Zeng J, Liu C-c, Zhu A-z, Chen X-y, Tan G-x, Liu G-x. Salinomycin inhibited proliferation and induced apoptosis of cisplatin-resistant human lung adenocarcinoma cell line A549/DDP.pdf. Chin J Pathophysiol. 2012;28:834–8.

    CAS  Google Scholar 

  26. Wu D et al. Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo. Biochem Biophys Res Commun. 2014;443(2):712–7.

    Article  CAS  PubMed  Google Scholar 

  27. Wang F et al. Salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo. PLoS One. 2012;7(12):e50638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Shin S-J et al. Salinomycin have antiproliferative and apoptotic effects on ovarian cancer stem-like cell. In: Proceedings of the 105th annual meeting of the american association for cancer research. 2014. Cancer Res 2014: 5–9.

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Acknowledgments

This Study was funded by the Ankara University BAP Project No: 13B3330001 and accepted as Master Thesis, by The Institute of Health Sciences.

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Correspondence to Fuat Kaplan or Fulya Teksen.

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Kaplan, F., Teksen, F. Apoptotic effects of salinomycin on human ovarian cancer cell line (OVCAR-3). Tumor Biol. 37, 3897–3903 (2016). https://doi.org/10.1007/s13277-015-4212-6

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  • DOI: https://doi.org/10.1007/s13277-015-4212-6

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