SpringerLink
Log in

Exploration of New Nickel and Copper(II) Complexes as Potential P53/Caspase 9 Activator in Human Colon Cancer Cell Line

  • Published:
Russian Journal of General Chemistry Aims and scope Submit manuscript

Abstract

The two new complexes, namely [NiU2(H2O)2]SO4, (NiU) and [CuU2(H2O)2]SO4, (CuU) [U = 5,6-diamino-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione monohydrate] were synthesized and characterized by elemental analysis, physicochemical, spectroscopic, (UV-visible, IR, ESI-MS, and XRD), thermal analysis and cyclic voltametric techniques. As showed in the data obtained, an octahedral geometry has been assigned for the two complexes. The data proved that the new complexes NiU and CuU have anticancer activities against colon cancer (HCT-116), epithelioid carcinoma (HeLa), and prostate adenocarcinoma (PC3) human cancer cell lines. The apoptotic pathway for both NiU and CuU complexes was via p53 elevation, which can arrest the cell cycle and activate the release of cytochrome c. The HCT-116 cells were treated with either NiU or CuU complexes had increased the production of caspase-9, which can activate the production of caspase-3 that degrades all the proteins in the cell, leading to apoptotic cell death. Consequently, the two complexes have promising anticancer activities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme
Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

REFERENCES

  1. Giaccone, G., Drugs, 2000, vol. 59, p. 9. https://doi.org/10.2165/00003495-200059004-00002

    Article  CAS  PubMed  Google Scholar 

  2. Tapiero, H., Townsend, D.M., and Tew, K.D., Biomed. Pharmacother., 2003, vol. 57, no. 9, p. 386. https://doi.org/10.1016/S0753-3322(03)00012-X

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Zamble, D., RSC Metallobiol., 2017. https://doi.org/10.1039/9781788010580-00001

  4. Santiago, P.H.O., Fujimori, M., Chagas, M.A.S., França, E.L., Honorio-França, A.C., and Gatto, C.C., Structural Chemistry, 2020, vol. 31, no. 1, p. 171. https://doi.org/10.1007/s11224-019-01379-w

    Article  CAS  Google Scholar 

  5. Denoyer, D., Masaldan, S., La Fontaine, S., and Cater, M.A., Metallomics, 2015, vol. 7, no. 11, p. 1459. https://doi.org/10.1039/c5mt00149h

    Article  CAS  PubMed  Google Scholar 

  6. Molinaro, C., Martoriati, A., Pelinski, L., and Cailliau, K., Cancers, 2020, vol. 12, no. 10, p. 2863. https://doi.org/10.3390/cancers12102863

    Article  CAS  PubMed Central  Google Scholar 

  7. Carcelli, M., Tegoni, M., Bartoli, J., Marzano, C., Pelosi, G., Salvalaio, M., Rogolino, D., and Gandin, V., Eur. J. Med. Chem., 2020, vol. 194, p. 112266. https://doi.org/10.1016/j.ejmech.2020.112266

    Article  CAS  PubMed  Google Scholar 

  8. Shi, X., Fang, H., Guo, Y., Yuan, H., Guo, Z., and Wang, X., J. Inorg. Biochem., 2019, vol. 190, p. 38. https://doi.org/10.1016/j.**orgbio.2018.10.003

    Article  CAS  PubMed  Google Scholar 

  9. Li, D.-D., Yagüe, E., Wang, L.-Y., Dai, L.-L., Yang, Z.-B., Zhi, S., Zhang, N., Zhao, X.-M., and Hu, Y.-H., ACS Medicinal Chemistry Letters, 2019, vol. 10, no. 9, p. 1328. https://doi.org/10.1021/acsmedchemlett.9b00284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rawajfeh, R.S., Awwadi, F.F., Bardaweel, S.K., and Hodali, H.A., J. Struct. Chem., 2020, vol. 61, no. 12, p. 1985. https://doi.org/10.1134/S0022476620120173

    Article  CAS  Google Scholar 

  11. Masaryk, L., Tesarova, B., Choquesillo-Lazarte, D., Milosavljevic, V., Heger, Z., and Kopel, P., J. Inorg. Biochem., 2021, vol. 217, p. 111395. https://doi.org/10.1016/j.**orgbio.2021.111395

    Article  CAS  PubMed  Google Scholar 

  12. Li, Y., Dong, J., Zhao, P., Hu, P., Yang, D., Gao, L., and Li, L., Bioinorg. Chem. Appl., 2020, vol. 2020, Article ID 8834859. https://doi.org/10.1155/2020/8834859

  13. Ahmad, S.N., Bahron, H., Tajuddin, A.M., and Ramasamy, K., Malaysian J. Fundam. Appl. Sci., 2019, vol. 15, no. 4, p. 613. https://doi.org/10.11113/mjfas.v15n4.1508

    Article  Google Scholar 

  14. Neethu, K., Sivaselvam, S., Theetharappan, M., Ranjitha, J., Bhuvanesh, N., Ponpandian, N., Neelakantan, M., and Kaveri, M., Inorg. Chim. Acta, 2021, vol. 524, p. 120419. https://doi.org/10.1016/j.ica.2021.120419

    Article  CAS  Google Scholar 

  15. Maikoo, S., Dingle, L.M.K., Chakraborty, A., Xulu, B., Edkins, A.L., and Booysen, I. N., Polyhedron, 2020, vol. 184, p. 114569. https://doi.org/10.1016/j.poly.2020.114569

    Article  CAS  Google Scholar 

  16. Alemayehu, Y.A., Ilhami, F.B., Manayia, A.H., and Cheng, C.-C., Acta Biomaterialia, 2021, vol. 129, p. 235. https://doi.org/10.1016/j.actbio.2021.05.044

    Article  CAS  PubMed  Google Scholar 

  17. Huang, C., Chen, S., Lai, C., Reneker, D.H., Qiu, H., Ye, Y., and Hou, H., Nanotechnology, 2006, vol. 17, no. 6, p. 1558. https://doi.org/10.1088/0957-4484/17/6/004

    Article  CAS  PubMed  Google Scholar 

  18. Krishnakumar, V. and Ramasamy, R., Indian J. Pure Appl. Phys., 2003, vol. 41, p. 258.

    CAS  Google Scholar 

  19. Mostafa, S.I., Kabil, M., Saad, E., and El-Asmy, A., J. Coord. Chem., 2006, vol. 59, no. 3, p. 279. https://doi.org/10.1080/00958970500266149

    Article  CAS  Google Scholar 

  20. Gupta, M. and Srivastava, M., Synth. React. Inorg. Met.-Org. Chem., 1996, vol. 26, no. 2, p. 305. https://doi.org/10.1080/00945719608004266

    Article  CAS  Google Scholar 

  21. Mabrouk, H., El-Asmy, A., Khalifa, M., and Zedan, M., Synth. React. Inorg. Met.-Org. Chem., 1996, vol. 26, no. 3, p. 423. https://doi.org/10.1080/00945719608005116

    Article  CAS  Google Scholar 

  22. Shoair, A.G.F., J. Coord. Chem., 2012, vol. 65, no. 20, p. 3511. https://doi.org/10.1080/00958972.2012.719079

    Article  CAS  Google Scholar 

  23. Li, W.-K., Zhou, G.-D., and Mak, T., Advanced Structural Inorganic Chemistry, OUP Oxford, 2008.

  24. Santos, L.M., Sarto, L. E., Bozza, G.F., and de Almeida, E.T., Revista Virtual De Quimica, 2014, vol. 6, no. 5, p. 1260. https://doi.org/10.5935/1984-6835.20140083

    Article  Google Scholar 

  25. Wu, L., Chen, Y., Pei, J., Tang, M., Wang, S., and Liu, Z., Chin. J. Chem., 2019, vol. 37, p. 834. https://doi.org/10.1002/cjoc.201900187

    Article  CAS  Google Scholar 

  26. Samy, F., Ramadan, A., Seleem, H., and Taha, A., Asian J. Chem., 2016, vol. 28, no. 12, p. 2650. https://doi.org/10.14233/ajchem.2016.20046

    Article  CAS  Google Scholar 

  27. Thirumaran, S. and Ramalingam, K., Transition Met. Chem., 2000, vol. 25, no. 1, p. 60. https://doi.org/10.1023/A:1007097629965

    Article  CAS  Google Scholar 

  28. Gökmeşe, E., Int. J. Electrochem. Sci, 2011, vol. 6, p. 103.

    Google Scholar 

  29. Hadjiliadis, N. and Sletten, Metal Complex–DNA Interactions, John Wiley & Sons, Ltd, Chichester, UK, 2009.

  30. Chaloner, P.A., J. Organomet. Chem., 1990, vol. 389, p. c35. https://doi.org/10.1016/0022-328x(90)85440-a

  31. Altomare, A., Cuocci, C., Giacovazzo, C., Moliterni, A., Rizzi, R., Corriero, N., and Falcicchio, A., J. Appl. Crystallogr., 2013, vol. 46, no. 4, p. 1231. https://doi.org/10.1107/S0021889813013113

    Article  CAS  Google Scholar 

  32. Kepert, D., Inorg. Chem., 1972, vol. 11, no. 7, p. 1561. https://doi.org/10.1021/ic50113a022

    Article  CAS  Google Scholar 

  33. Rutherford, T.J., Reitsma, D.A., and Keene, F. R., J. Chem. Soc., Dalton Trans., 1994, no. 24, p. 3659. https://doi.org/10.1039/DT9940003659

    Article  Google Scholar 

  34. Iranzo, O., Bioorg. Chem., 2011, vol. 39, no. 2, p. 73. https://doi.org/10.1016/j.bioorg.2011.02.001

    Article  CAS  PubMed  Google Scholar 

  35. Jia, L., Xu, X.-M., Xu, J., Chen, L.-H., Jiang, P., Cheng, F.-X., Lu, G.-N., Wang, Q., Wu, J.-C., and Tang, N., Chem. Pharm. Bull., 2010, vol. 58, no. 8, p. 1003. https://doi.org/10.1248/cpb.58.1003

    Article  CAS  Google Scholar 

  36. Reinhardt, C.G. and Krugh, T.R., Biochemistry, 1978, vol. 17, no. 23, p. 4845. https://doi.org/10.1021/bi00616a001

    Article  CAS  PubMed  Google Scholar 

  37. Yıldız, M., Tan, E., Demir, N., Yıldırım, N., Ünver, H., Kiraz, A., and Mestav, B., Russ. J. Gen. Chem., 2015, vol. 85, no. 9, p. 2149. https://doi.org/10.1134/S1070363215090200

    Article  CAS  Google Scholar 

  38. Lakshmipraba, J., Arunachalam, S., Solomon, R.V., Venuvanalingam, P., Riyasdeen, A., Dhivya, R., and Akbarsha, M.A., J. Biomol. Struct. Dyn., 2015, vol. 33, no. 4, p. 877. https://doi.org/10.1080/07391102.2014.918523

    Article  CAS  PubMed  Google Scholar 

  39. Hu, X., Liu, N.-Y., Deng, Y.-Q., Wang, S., Liu, T., and Liu, X.-W., Molecules, 2021, vol. 26, no. 11, p. 3471. https://doi.org/10.3390/molecules26113471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mydhili, S.P., Venkata Ramana Reddy, C., Sireesha, B., and Sreekanth, S., Res. J. Chem. Environ., 2021, vol. 25, p. 143. https://doi.org/10.25303/2511rjce143152

    Article  CAS  Google Scholar 

  41. Zhou, C.-Y., Wu, Y.-B., and Yang, P., Biochemistry (Moscow), 2010, vol. 75, no. 4, p. 505. https://doi.org/10.1134/S0006297910040152

    Article  CAS  Google Scholar 

  42. Lemasters, J., J. Bioenerg. Biomembr., 1999, vol. 31, p. 305. https://doi.org/10.1023/A:1005419617371

    Article  CAS  PubMed  Google Scholar 

  43. Proskuryakov, S.Y. and Gabai, V.L., Curr. Pharm. Design, 2010, vol. 16, no. 1, p. 56. https://doi.org/10.2174/138161210789941793

    Article  CAS  Google Scholar 

  44. Arung, E.T., Wicaksono, B.D., Handoko, Y.A., Kusuma, I.W., Yulia, D., and Sandra, F., Trop. J. Pharm. Res., 2009, vol. 8, no. 4. https://doi.org/10.4314/tjpr.v8i4.45223

  45. Ting-Wen, C., Shih-Chao, L., Su, J.-H., Yu-Kuo, C., Chi-Chien, L., and Hong-Lin, C., BMC Complem. Med. Ther., 2017, vol. 17. https://doi.org/10.1186/s12906-017-1583-9

  46. Göktürk, T., Topkaya, C., Sakallı Çetin, E., and Güp, R., Chem. Papers, 2022, vol. 76, no. 4, p. 2093. https://doi.org/10.1007/s11696-021-02005-y

    Article  CAS  Google Scholar 

  47. Green, D.R. and Kroemer, G., Nature, 2009, vol. 458, no. 7242, p. 1127. https://doi.org/10.1038/nature07986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Li, T., Kon, N., Jiang, L., Tan, M., Ludwig, T., Zhao, Y., Baer, R., and Gu, W., Cell, 2012, vol. 149, no. 6, p. 1269. https://doi.org/10.1016/j.cell.2012.04.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hussain, S., Schwank, J., Staib, F., Wang, X., and Harris, C., Oncogene, 2007, vol. 26, no. 15, p. 2166. https://doi.org/10.1038/sj.onc.1210279

    Article  CAS  PubMed  Google Scholar 

  50. Jiang, X., Annu. Rev. Biochem, 2004, vol. 73, p. 87. https://doi.org/10.1146/annurev.biochem.73.011303.073706

    Article  CAS  PubMed  Google Scholar 

  51. Lavrik, I.N., Golks, A., and Krammer, P.H., J. Clin. Invest., 2005, vol. 115, no. 10, p. 2665. https://doi.org/10.1172/JCI26252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Jiang, X. and Wang, X., J. Biol. Chem., 2000, vol. 275, no. 40, p. 31199. https://doi.org/10.1074/jbc.C000405200

    Article  CAS  PubMed  Google Scholar 

  53. Rochford, G., Molphy, Z., Kavanagh, K., McCann, M., Devereux, M., Kellett, A., and Howe, O., Metallomics, 2020, vol. 12, no. 1, p. 65. https://doi.org/10.1039/c9mt00187e

    Article  CAS  PubMed  Google Scholar 

  54. Ott, M., Proc Natl Acad Sci USA, 2002, vol. 99, p. 1259. https://doi.org/10.1073/pnas.241655498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cory, A., Owen, T., and Barltrop, J., Cancer Commun., 1991, vol. 3, p. 207. https://doi.org/10.3727/095535491820873191

    Article  CAS  PubMed  Google Scholar 

  56. Elsayed, A.M., Sherif, N.M., Hassan, N.S., Althobaiti, F., Hanafy, N.A., and Sahyon, H.A., Int. J. Biol. Macromol., 2021, vol. 185, p. 134. https://doi.org/10.1016/j.ijbiomac.2021.06.085

    Article  CAS  PubMed  Google Scholar 

  57. Sahyon, H.A. and Al-Harbi, S.A., Food Chem. Toxicol., 2020, vol. 135, p. 111045. https://doi.org/10.1016/j.fct.2019.111045

    Article  CAS  PubMed  Google Scholar 

  58. Elsayed, S.A., Harrypersad, S., Sahyon, H.A., El-Magd, M.A., and Walsby, C.J., Molecules, 2020, vol. 25, no. 18, p. 4284. https://doi.org/10.3390/molecules25184284

    Article  CAS  PubMed Central  Google Scholar 

  59. Sahyon, H.A.E., Ramadan, E.N., Althobaiti, F., and Mashaly, M., Naunyn-Schmiedeberg’s Arch. Pharmacol., 2022, vol. 395, no. 2, p. 227. https://doi.org/10.1007/s00210-021-02174-3

    Article  CAS  Google Scholar 

Download references

Funding

This work was funded by Taif University Researchers Supporting Project no. TURSP-2020/197 (Taif University, Taif, Saudi Arabia).

Author information

Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Kafrelsheikh University, 33516, Kafrelsheikh, Egypt

    H. A. Sahyon

  2. Department of Science and Technology, University College – Ranyah, Taif University, 21975, Taif, Saudi Arabia

    A. G. F. Shoair

  3. Department of Biotechnology, College of Science, Taif University, 21944, Taif, Saudi Arabia

    F. Althobaiti

  4. Department of Chemistry, College of Sciences and Humanities Studies (Girls Section), Hawtat Bani Tamim, Prince Sattam Bin Abdulaziz University, 11149, Al-Kharj, Saudi Arabia

    M. M. A. H. Shanab

  5. Chemistry Department, Faculty of Science, Damietta University, 34517, Damietta, Egypt

    M. A. Helal

  6. Chemistry Department, Faculty of Science, Zagazig University, 44519, Zagazig, Egypt

    A. M. Fathy

  7. Clinical Laboratory Science Department, Turabah University College, Taif University, 21995, Taif, Saudi Arabia

    A. Aldhahrani

Authors
  1. H. A. Sahyon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. G. F. Shoair
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. Althobaiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. M. A. H. Shanab
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. A. Helal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. M. Fathy
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Aldhahrani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. A. Sahyon.

Ethics declarations

No conflict of interest was declared by the authors.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sahyon, H.A., Shoair, A.G.F., Althobaiti, F. et al. Exploration of New Nickel and Copper(II) Complexes as Potential P53/Caspase 9 Activator in Human Colon Cancer Cell Line. Russ J Gen Chem 92, 2058–2069 (2022). https://doi.org/10.1134/S1070363222100206

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1070363222100206

Keywords:

Search

Navigation