Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells
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...
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Dove Medical Press
2018
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| Online Access: | http://eprints.um.edu.my/20607/ https://doi.org/10.2147/DDDT.S141925 |
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| author | Subramaniam, Menaga Liew, Su Ki In, Lionel L.A. Awang, Khalijah Ahmed, Niyaz Nagoor, Noor Hasima |
| author_facet | Subramaniam, Menaga Liew, Su Ki In, Lionel L.A. Awang, Khalijah Ahmed, Niyaz Nagoor, Noor Hasima |
| author_sort | Subramaniam, Menaga |
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| content_provider | Universiti Malaya |
| content_source | UM Research Repository |
| continent | Asia |
| country | Malaysia |
| description | 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. |
| format | Article |
| id | my.um.eprints-20607 |
| institution | Universiti Malaya |
| publishDate | 2018 |
| publisher | Dove Medical Press |
| record_format | eprints |
| spelling | my.um.eprints-206072019-03-05T02:54:13Z http://eprints.um.edu.my/20607/ Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells Subramaniam, Menaga Liew, Su Ki In, Lionel L.A. Awang, Khalijah Ahmed, Niyaz Nagoor, Noor Hasima Q Science (General) QD Chemistry QH Natural history R Medicine 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. Dove Medical Press 2018 Article PeerReviewed 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 https://doi.org/10.2147/DDDT.S141925 <https://doi.org/10.2147/DDDT.S141925>. https://doi.org/10.2147/DDDT.S141925 doi:10.2147/DDDT.S141925 |
| spellingShingle | Q Science (General) QD Chemistry QH Natural history R Medicine Subramaniam, Menaga Liew, Su Ki In, Lionel L.A. Awang, Khalijah Ahmed, Niyaz Nagoor, Noor Hasima Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells |
| title | Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells |
| title_full | Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells |
| title_fullStr | Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells |
| title_full_unstemmed | Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells |
| title_short | Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells |
| title_sort | inactivation of nuclear factor κb by mip-based drug combinations augments cell death of breast cancer cells |
| topic | Q Science (General) QD Chemistry QH Natural history R Medicine |
| url | http://eprints.um.edu.my/20607/ https://doi.org/10.2147/DDDT.S141925 |
| url_provider | http://eprints.um.edu.my/ |