title: Mechanism of Action of the Novel Nickel(II) Complex in Simultaneous Reactivation of the Apoptotic Signaling Networks Against Human Colon Cancer Cells.
abstract: The aim of this study was to evaluate the cytotoxic potential of a novel nickel(II) complex (NTC) against WiDr and HT-29 human colon cancer cells by determining the IC50 using the standard MTT assay. The NTC displayed a strong suppressive effect on colon cancer cells with an IC50 value of 6.07 ± 0.22 μM and 6.26 ± 0.13 μM against WiDr and HT-29 respectively, after 24 h of treatment. Substantial reduction in the mitochondrial membrane potential and increase in the release of cytochrome c from the mitochondria directed the induction of the intrinsic apoptosis pathway by the NTC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. The NTC was also shown to activate the extrinsic pathway of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of the current work indicates that NTC possess a potent cancer cell abolishing activity by simultaneous induction of intrinsic and extrinsic pathways of apoptosis in colon cancer cell lines.
authors: Department of Pharmacology, Faculty of Medicine, University of MalayaKuala Lumpur, Malaysia; Drug and Research Unit, Department of Pathology, Hospital Kuala LumpurKuala Lumpur, Malaysia.
authors: Nima
authors: N
authors: Samie
authors: Department of Pharmacology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia.
authors: Batoul Sadat
authors: BS
authors: Haerian
authors: Department of Molecular Medicine, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia.
authors: Sekaran
authors: S
authors: Muniandy
authors: Department of Chemistry, Faculty of Science, University of Malaya Kuala Lumpur, Malaysia.
authors: Anita
authors: A
authors: Marlina
authors: Department of Molecular Medicine, Faculty of Medicine, University of MalayaKuala Lumpur, Malaysia; Faculty of Medicine, University of Malaya Centre for Proteomics Research, University of MalayaKuala Lumpur, Malaysia.
authors: M S
authors: MS
authors: Kanthimathi
authors: Department of Chemistry, Faculty of Science, University of Malaya Kuala Lumpur, Malaysia.
authors: Norbani B
authors: NB
authors: Abdullah
authors: Department of Environmental and Industrial Biotechnology, National Institute of Genetic Engineering and Biotechnology Tehran, Iran.
authors: Gholamreza
authors: G
authors: Ahmadian
authors: Drug and Research Unit, Department of Pathology, Hospital Kuala Lumpur Kuala Lumpur, Malaysia.
authors: Raja E R
authors: RE
authors: Aziddin
keywords: NF-κB; apoptosis; cell cycle arrest; colon cancer; nickel(II) complex