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Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells

Authors Subramaniam M, Liew SK, In LLA, Awang K, Ahmed N, Nagoor NH

Received 16 May 2017

Accepted for publication 21 July 2017

Published 1 May 2018 Volume 2018:12 Pages 1053—1063


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Anastasios Lymperopoulos

Menaga Subramaniam,1 Su Ki Liew,1 Lionel LA In,2 Khalijah Awang,3,4 Niyaz Ahmed,5 Noor Hasima Nagoor1,6

1Institute of Biological Science (Genetics & Molecular Biology), Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 2Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia; 3Centre for Natural Product Research and Drug Discovery (CENAR), University of Malaya, Kuala Lumpur, Malaysia; 4Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; 5Pathogen Biology Laboratory, Department of Biotechnology and Bioinformatics, University of Hyderabad, Hyderabad, India; 6Centre for Research in Biotechnology for Agriculture (CEBAR), University of Malaya, Kuala Lumpur, Malaysia

Background: Drug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects.
Materials and methods: In the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1'S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP) and cisplatin (CDDP) against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB) and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression
Results: All combinations confirmed intrinsic apoptosis activation and NF-κB inactivation.
Conclusion: Double and triple combination regimens that target induction of the same death mechanism with reduced dosage of each drug could potentially be clinically beneficial in reducing dose-related toxicities.

Mycobacterium indicus pranii, 1'S-1'-acetoxychavicol acetate, drug combination, nuclear factor κB

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