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

Subramaniam, Menaga and Liew, Su Ki and In, Lionel L.A. and Awang, Khalijah and Ahmed, Niyaz and Nagoor, Noor Hasima (2018) Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells. Drug Design, Development and Therapy, 12. pp. 1053-1063. ISSN 1177-8881, DOI

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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.

Item Type: Article
Funders: Ministry of Science, Technology and Innovation (MOSTI) through the Science Fund (PROJECT NO 02-01-03-SF0863 and 02-02-22-SF0011), UCSI University Pioneer Scientist Initiative Fund (PSIF) (Proj-In-FAS-041)
Uncontrolled Keywords: Mycobacterium indicus pranii; 1'S-1'-acetoxychavicol acetate; drug combination; nuclear factor κB
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Q Science > QH Natural history
R Medicine
Divisions: Faculty of Medicine
Faculty of Science > Department of Chemistry
Faculty of Science > Institute of Biological Sciences
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 05 Mar 2019 02:54
Last Modified: 05 Mar 2019 02:54

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