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Studies of the anticancer activities of ruthenium(II) polypyridyl complexes toward human hepatocellular carcinoma BEL-7402 cells

  • Zhen-Hua LiangEmail author
  • Ya-Ning Wang
  • Zhi-Wei Xiong
  • Xiao-Yan Chen
  • Lin Tong
Article
  • 12 Downloads

Abstract

Two ruthenium(II) polypyridyl complexes formulated as [Ru(bpy)2(THPDP)](PF6)2 (1) and [Ru(ttbpy)2(THPDP)](PF6)2 (ttbpy = 4,4ʹ-ditertiary butyl-2,2ʹ-bipyridine) (2) were synthesized and characterized by elemental analysis, 1H NMR, 13C NMR and UV–Vis spectra. The cytotoxic activities of the complexes against cancer cell lines BEL-7402, A549, SGC-7901, HeLa and normal NIH3T3 cells were investigated by 3-(4,5-dimethylthiazole)-2,5-diphenyltetrazolium bromide (MTT) methods. The complexes show moderate cytotoxicity toward BEL-7402 and HeLa cells. The changes in mitochondrial membrane potential, intracellular Ca2+ and reactive oxygen species were studied by fluorescence microscopy. Both complexes can increase intracellular Ca2+ concentrations and ROS levels and induce a decrease in mitochondrial membrane potential. They also inhibit cell invasion and suppress cell proliferation at the G0/G1 phase. Additionally, they activate caspase 3, cleave PARP and regulate the expression of Bcl-2 family proteins. In short, the complexes induce apoptosis in BEL-7402 cells through a ROS-mediated mitochondria dysfunction pathway.

Notes

Acknowledgements

We are grateful to Science and Technology Project of Jiangxi Education Department in 2017 (No GJJ171024) and Jiangxi University of Technology for financial support.

References

  1. 1.
    Rosenberg B, VanCamp L, Trosko JE, Mansour VH (1969) Nature 222:385–386CrossRefGoogle Scholar
  2. 2.
    Pasetto LM, Andrea MRD, Brandes AA, Rossi E, Monfardini S (2006) Crit Rev Oncol/Hematol 60:59–75CrossRefGoogle Scholar
  3. 3.
    Hall MD, Telma KA, Chang KE, Lee TD, Madigan JP, Lloyd JR, Goldlust IS, Hoeschele JD, Gottesman MM (2014) Cancer Res 74:3913–3922CrossRefGoogle Scholar
  4. 4.
    Kelland L (2007) Nat Rev Cancer 7:573–584CrossRefGoogle Scholar
  5. 5.
    Siddik ZH (2003) Oncogene 22:7265–7279CrossRefGoogle Scholar
  6. 6.
    Li YM, Wu Q, Yu GN, Li L, Zhao XH, Huang XT, Mei WJ (2019) Eur J Med Chem 164:282–291CrossRefGoogle Scholar
  7. 7.
    Wan D, Tang B, Wang YJ, Guo BH, Yin H, Yi QY, Liu YJ (2017) Eur J Med Chem 139:180–189CrossRefGoogle Scholar
  8. 8.
    Wan D, Lai SH, Zeng CC, Zhang C, Tang B, Liu YJ (2017) J Inorg Biochem 173:1–11CrossRefGoogle Scholar
  9. 9.
    Tang B, Wan D, Lai SH, Yang HH, Zhang C, Wang XZ, Zeng CC, Liu YJ (2017) J Inorg Biochem 173:93–104CrossRefGoogle Scholar
  10. 10.
    Tang B, Shen F, Wan D, Guo BH, Wang YJ, Yi QY, Liu YJ (2017) RSC Adv 7:34945–34958CrossRefGoogle Scholar
  11. 11.
    Ypsilantis K, Plakatouras JC, Manos MJ, Kourtellaris A, Markopoulos G, Kolettas E, Garoufis A (2018) Dalton Trans 47:3549–3567CrossRefGoogle Scholar
  12. 12.
    Chen JC, Zhang Y, Li GD, Peng F, Jie XM, She J, Dongye GZ, Zou ZL, Rong SW, Chen LM (2018) J Biol Inorg Chem 23:261–275CrossRefGoogle Scholar
  13. 13.
    Cao WQ, Zheng WJ, Chen TF (2015) Sci Rep-UK 5:9157CrossRefGoogle Scholar
  14. 14.
    Zeng CC, Lai SH, Yao JH, Zhang C, Yin H, Li W, Han BJ, Liu YJ (2016) Eur J Med Chem 122:118–126CrossRefGoogle Scholar
  15. 15.
    Tang B, Wan D, Wang YJ, Yi QY, Guo BH, Liu YJ (2018) Eur J Med Chem 145:302–314CrossRefGoogle Scholar
  16. 16.
    Sullivan BP, Salmon DJ, Meyer TJ (1978) Inorg Chem 17:3334–3341CrossRefGoogle Scholar
  17. 17.
    Mosmann T (1983) J Immunol Methods 65:55–63CrossRefGoogle Scholar
  18. 18.
    Zhang C, Han BJ, Zeng CC, Lai SH, Li W, Tang B, Wan D, Jiang GB, Liu YJ (2016) J Inorg Biochem 157:62–72CrossRefGoogle Scholar
  19. 19.
    McBride HM, Neuspiel M, Wasiak S (2006) Curr Biol 16:R551–R560CrossRefGoogle Scholar
  20. 20.
    Henze K, Martin W (2002) Nature 426:127–128CrossRefGoogle Scholar
  21. 21.
    Laver DR (2007) Biophys J 92:3541–3555CrossRefGoogle Scholar
  22. 22.
    Cadenas E, Davies KJA (2000) Free Radical Biol Med 29:222–230CrossRefGoogle Scholar
  23. 23.
    Chou CC, Yang JS, Lu HS, Ip SW, Lo C, Wu CC, Lin JP, Tang NY, Chung JG, Chou MJ, Teng YH, Chen DR (2010) Arch Pharm Res 33:1181–1191CrossRefGoogle Scholar
  24. 24.
    Adams JM (2003) Genes Dev 17:2481–2495CrossRefGoogle Scholar
  25. 25.
    Duriez P, Shah GM (1997) Biochem Cell Biol 75:337–349CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Pharmacy DivisionPingxiang People’s HospitalAnyuan District, Pingxiang CityPeople’s Republic of China
  2. 2.School of NursingJiangxi University of TechnologyNanchangPeople’s Republic of China

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