Ternary Copper (II) Complex Induced Apoptosis and Cell Cycle Arrest in Colorectal Cancer Cells.

Autor:	Arikrishnan S; School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Loh JS; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Teo XW; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Bin Norizan F; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Low ML; Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000, Kuala Lumpur, Malaysia., Lee SH; School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.; Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Foo JB; School of Pharmacy, Faculty of Health and Medical Sciences, Taylor\'s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.; Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia., Tor YS; School of Biosciences, Faculty of Health and Medical Sciences, Taylor\'s University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.; Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health & Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2022; Vol. 22 (5), pp. 999-1011.
DOI:	10.2174/1871520621666210708100019
Abstrakt:	Background: The lack of specificity, severe side effects, and development of drug resistance have largely limited the use of platinum-based compounds in cancer treatment. Therefore, copper complexes have emerged as potential alternatives to platinum-based compounds. Objective: Ternary copper (II) complex incorporated with 1-10-phenanthroline and L-tyrosine was investigated for its anti-cancer effects in HT-29 colorectal cancer cells. Methods: Cytotoxic effects of ternary copper (II) complex in HT-29 cells was evaluated using MTT assay, Real-Time Cell Analysis (RTCA) and lactate dehydrogenase (LDH) assay. Cell cycle analysis was performed using flow cytometry. Apoptosis induction was studied by Annexin V-FITC/Propidium Iodide (PI) staining and mitochondrial membrane potential analysis (JC-10 staining) using flow cytometry. Intracellular Reactive Oxygen Species (ROS) were detected by DCFH-DA assay. The expression of proteins involved in the apoptotic signalling pathway (p53, caspases, and PARP-1) was evaluated by western blot analysis. Results: Ternary copper (II) complex reduced the cell viability of HT-29 cells in a time- and dose-dependent manner, with IC50 of 2.4 ± 0.4 and 0.8 ± 0.04 μM at 24 and 48 hours, respectively. Cell cycle analysis demonstrated induction of S-phase cell cycle arrest. Morphological evaluation and Annexin V-FITC/PI flow cytometry analysis confirmed induction of apoptosis that was further supported by cleavage and activation of caspase-8, caspase-9, caspase-3, and PARP- 1. Mutant p53 was also downregulated in a dose-dependent manner. No LDH release, mitochondrial membrane potential disruption, and ROS production were observed. Conclusion: Ternary copper (II) complex holds great potential to be developed for colorectal cancer treatment. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu