AUTHOR=Samie Nima , Haerian Batoul Sadat , Muniandy Sekaran , Marlina Anita , Kanthimathi M. S. , Abdullah Norbani B. , Ahmadian Gholamreza , Aziddin Raja E. R. 

TITLE=Mechanism of Action of the Novel Nickel(II) Complex in Simultaneous Reactivation of the Apoptotic Signaling Networks Against Human Colon Cancer Cells

JOURNAL=Frontiers in Pharmacology

VOLUME=6

YEAR=2016

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2015.00313

DOI=10.3389/fphar.2015.00313

ISSN=1663-9812

ABSTRACT=<p>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 IC<sub>50</sub> using the standard MTT assay. The NTC displayed a strong suppressive effect on colon cancer cells with an IC<sub>50</sub> 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.</p>