Research Article

Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231

Volume: 41 Number: 4 December 29, 2020
EN

Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231

Abstract

Polo-like kinase 1 (PLK1) regulates various steps of mitosis and aberrantly expressed in several tumor types. As elevated levels of PLK1 contributes to tumorigenesis and poor prognosis, specific inhibition of PLK1 has garnered increasing attention in recent years in anticancer studies. The objective of this study was to examine cytotoxic, apoptotic, and DNA-damaging potentials of SBE13, a PLK1 inhibitor, against MDA-MB-231 breast cancer cells. The regulatory efficacy of SBE13 on cell cycle arrest was also determined. Cytotoxicity of SBE13 was assessed via XTT assay. Apoptosis, cell cycle distribution, and DNA damage response were also examined using the flow cytometry assay. The results revealed that SBE13 had a dose-dependent cytotoxic effect in MDA-MB-231 cells. This compound has also induced cell cycle arrest at the G2/M point and significantly promoted apoptosis and DNA damage response in MDA-MB-231 cells. Collectively, these data pointed out that SBE13 can be regarded as a suitable candidate for the therapy of breast cancer. However, further studies are required to consolidate the anticancer activity of SBE13.

Keywords

PLK1 inhibition, SBE13, Breast Cancer, Apoptosis, DNA damage

Supporting Institution

Cumhuriyet University Scientific Research Project (CUBAP)

Project Number

ECZ-045

References

  1. [1] Siegel R.L., Miller K.D., Jemal A. Cancer statistics, 2019, CA Cancer J Clin., 69(1) (2019) 7-34.
  2. [2] Ergul M., Bakar-Ates F. RO3280: A Novel PLK1 Inhibitor, Suppressed the Proliferation of MCF-7 Breast Cancer Cells Through the Induction of Cell Cycle Arrest at G2/M Point, Anticancer Agents Med Chem., 19(15) (2019) 1846-1854.
  3. [3] Howell A., Anderson A.S., Clarke R.B., Duffy S.W., Evans D.G., Garcia-Closas M., Gescher A.J., Key T.J., Saxton J.M., Harvie, M.N. Risk determination and prevention of breast cancer, Breast cancer research: BCR, 16(5) (2014) 446.
  4. [4] Wu M., Wang Y., Yang D., Gong Y., Rao F., Liu R., Danna Y., Li J., Fan J., Chen J., Zhang W., Zhan, Q.A PLK1 kinase inhibitor enhances the chemosensitivity of cisplatin by inducing pyroptosis in oesophageal squamous cell carcinoma, EBioMedicine, 41 (2019) 244–255. [5] de Cárcer G., Venkateswaran S. V., Salgueiro L., El Bakkali A., Somogyi K., Rowald K., Montañés, P., Sanclemente M., Escobar B., de Martino A., McGranahan N., Malumbres M., Sotillo, R. Plk1 overexpression induces chromosomal instability and suppresses tumor development, Nature communications, 9(1) (2018) 3012.
  5. [6] Smith L., Farzan R., Ali S., Buluwela L., Saurin A. T., & Meek D.W. The responses of cancer cells to PLK1 inhibitors reveal a novel protective role for p53 in maintaining centrosome separation, Scientific reports, 7(1) (2017) 16115.
  6. [7] Wang N.N., Li Z.H., Zhao H., Tao Y. F., Xu L. X., Lu J., Cao L., Du X. J., Sun L. C., Zhao W. L., Xiao P. F., Fang F., Su G. H., Li Y. H., Li G., Li Y. P., Xu Y. Y., Zhou H. T., Wu Y., Jin M. F., Pan J. Molecular targeting of the oncoprotein PLK1 in pediatric acute myeloid leukemia: RO3280, a novel PLK1 inhibitor, induces apoptosis in leukemia cells, International journal of molecular sciences, 16(1) (2015) 1266–1292.
  7. [8] Choi M., Kim W., Cheon M. G., Lee C. W., & Kim J.E. Polo-like kinase 1 inhibitor BI2536 causes mitotic catastrophe following activation of the spindle assembly checkpoint in non-small cell lung cancer cells, Cancer letters, 357(2) (2015) 591–601.
  8. [9] Keppner S., Proschak E., Schneider G., Spänkuch B. SBE13, a newly identified inhibitor of inactive polo-like kinase 1, J Cheminform. (2010) 2(Suppl 1) P54.
  9. [10] Keppner S., Proschak E., Kaufmann M., Strebhardt K., Schneider G., & Spänkuch B. Biological impact of freezing Plk1 in its inactive conformation in cancer cells, Cell cycle, 9(4) (2010) 761–773.
  10. [11] Keppner S., Proschak E., Schneider G., & Spänkuch B. Identification and validation of a potent type II inhibitor of inactive polo-like kinase 1, ChemMedChem, 4(11) (2009) 1806–1809.
APA
Ergül, M. (2020). Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231. Cumhuriyet Science Journal, 41(4), 802-807. https://doi.org/10.17776/csj.774286
AMA
1.Ergül M. Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231. CSJ. 2020;41(4):802-807. doi:10.17776/csj.774286
Chicago
Ergül, Mustafa. 2020. “Investigation of Potential DNA Damaging and Apoptotic Effects of PLK1 Inhibitor SBE13 in Breast Cancer Cell Line MDA-MB-231”. Cumhuriyet Science Journal 41 (4): 802-7. https://doi.org/10.17776/csj.774286.
EndNote
Ergül M (December 1, 2020) Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231. Cumhuriyet Science Journal 41 4 802–807.
IEEE
[1]M. Ergül, “Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231”, CSJ, vol. 41, no. 4, pp. 802–807, Dec. 2020, doi: 10.17776/csj.774286.
ISNAD
Ergül, Mustafa. “Investigation of Potential DNA Damaging and Apoptotic Effects of PLK1 Inhibitor SBE13 in Breast Cancer Cell Line MDA-MB-231”. Cumhuriyet Science Journal 41/4 (December 1, 2020): 802-807. https://doi.org/10.17776/csj.774286.
JAMA
1.Ergül M. Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231. CSJ. 2020;41:802–807.
MLA
Ergül, Mustafa. “Investigation of Potential DNA Damaging and Apoptotic Effects of PLK1 Inhibitor SBE13 in Breast Cancer Cell Line MDA-MB-231”. Cumhuriyet Science Journal, vol. 41, no. 4, Dec. 2020, pp. 802-7, doi:10.17776/csj.774286.
Vancouver
1.Mustafa Ergül. Investigation of potential DNA damaging and apoptotic effects of PLK1 inhibitor SBE13 in breast cancer cell line MDA-MB-231. CSJ. 2020 Dec. 1;41(4):802-7. doi:10.17776/csj.774286