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

H. A. Sahyona, *, A. G. F. Shoairb, F. Althobaitic, M. M. A. H. Shanabd, M. A. Helale, A. M. Fathyf, and A. Aldhahranig

aChemistry Department, Faculty of Science, Kafrelsheikh University, Kafrelsheikh, 33516 Egypt

bDepartment of Science and Technology, University College – Ranyah, Taif University, Taif, 21975 Saudi Arabia

cDepartment of Biotechnology, College of Science, Taif University, Taif, 21944 Saudi Arabia

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

eChemistry Department, Faculty of Science, Damietta University, Damietta, 34517 Egypt

fChemistry Department, Faculty of Science, Zagazig University, Zagazig, 44519 Egypt

gClinical Laboratory Science Department, Turabah University College, Taif University, Taif, 21995 Saudi Arabia

email: *heba_sahuon@sci.kfs.edu.eg

Received 23 May, 2022

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.

Keywords: nickel(II), copper(II) complexes, DNA binding, P53, cytochrome C, caspase-9

DOI: 10.1134/S1070363222100206