Mechanism of action of the novel nickel(II) complex in simultaneous reactivation of the apoptotic signaling networks against human colon cancer cells

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Abstract

© 2016 Samie, Haerian, Muniandy, Marlina, Kanthimathi, Abdullah, Ahmadian and Aziddin.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.

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Samie, N., Haerian, B. S., Muniandy, S., Marlina, A., Kanthimathi, M. S., Abdullah, N. B., … Aziddin, R. E. R. (2016). Mechanism of action of the novel nickel(II) complex in simultaneous reactivation of the apoptotic signaling networks against human colon cancer cells. Frontiers in Pharmacology, 6(JAN). https://doi.org/10.3389/fphar.2015.00313

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