Mechanism of Action of the Novel Nickel(II) Complex in Simultaneous Reactivation of the Apoptotic Signaling Networks Against Human Colon Cancer Cells
Authors: Nima Samie
Norbani B Abdullah
Anita Marlina
Batoul Sadat Haerian
M S Kanthimathi
Raja E R Aziddin
Sekaran Muniandy
Gholamreza Ahmadian
Journal: Frontiers in Pharmacology (2016)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: NF-κB; apoptosis; cell cycle arrest; colon cancer; nickel(II) complex.
Affiliations: Department of Pharmacology, Faculty of Medicine, University of MalayaKuala Lumpur, Malaysia; Drug and Research Unit, Department of Pathology, Hospital Kuala LumpurKuala Lumpur, Malaysia., Department of Pharmacology, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia., Department of Molecular Medicine, Faculty of Medicine, University of Malaya Kuala Lumpur, Malaysia., Department of Chemistry, Faculty of Science, University of Malaya Kuala Lumpur, Malaysia., 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., Department of Environmental and Industrial Biotechnology, National Institute of Genetic Engineering and Biotechnology Tehran, Iran., Drug and Research Unit, Department of Pathology, Hospital Kuala Lumpur Kuala Lumpur, Malaysia.

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. 

Retracted: No

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 On June 29, 2016, the article was retracted: https: www.frontiersin.org articles 10.3389 fphar.2016.00199 full From the Retraction Notice:  The Journal and Authors retract the 28 January 2016 article cited above for the following reasons: Following online criticisms of the published paper, an investigation at the journal has confirmed the manipulation and duplication of data, and a level of image processing that is not compliant with the journalu2019s policies on image data integrity. Further, a post-publication cross-check screening revealed significant overlap with another manuscript submitted by the authors to another journal. While all manuscripts submitted to Frontiers undergo cross-check screening, the article cited below was in review in parallel with the Frontiers article and thus the overlap was not apparent until publication (Samie et al., 2016). ,