Anti-Cancer Effects of Synergistic Drug–Bacterium Combinations on Induced Breast Cancer in BALB/c Mice

Subramaniam, Menaga and Arshad, Norhafiza Mohd and Mun, Kein Seong and Malagobadan, Sharan and Awang, Khalijah and Nagoor, Noor Hasima (2019) Anti-Cancer Effects of Synergistic Drug–Bacterium Combinations on Induced Breast Cancer in BALB/c Mice. Biomolecules, 9 (10). p. 626. ISSN 2218-273X, DOI https://doi.org/10.3390/biom9100626.

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Official URL: https://doi.org/10.3390/biom9100626

Abstract

Cancer development and progression are extremely complex due to the alteration of various genes and pathways. In most cases, multiple agents are required to control cancer progression. The purpose of this study is to investigate, using a mouse model, the synergistic interactions of anti-cancer agents, 1′-S-1′-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP), and cisplatin (CDDP) in double and triple combinations to treat chemo-sensitize and immune-sensitize breast cancer. Changes in tumor volume and body weight were monitored. Organs were harvested and stained using hematoxylin-eosin for histopathological assessment. Milliplex enzyme-linked immunosorbent assay (ELISA) was performed to determine cytokine levels, while immunohistochemistry (IHC) was conducted on tumor biopsies to verify systemic drug effects. In vivo mouse models showed tumor regression with maintenance of regular body weight for all the different treatment regimens. IHC results provided conclusive evidence indicating that combination regimens were able to down-regulate nuclear factor kappa-B activation and reduce the expression of its regulated pro-inflammatory proteins. Reduction of pro-inflammatory cytokines (e.g., IL-6, TNF-α, and IFN-γ) levels were observed when using the triple combination, which indicated that the synergistic drug combination was able to significantly control cancer progression. In conclusion, ACA, MIP, and CDDP together serve as promising candidates for further development and for subsequent clinical trials against estrogen-sensitive breast cancer. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Article
Funders: Ministry of Science, Technology, and Innovation (MOSTI) through the Science Fund (Project No. 02-01-03-SF0863), Centre for Research in Biotechnology for Agriculture (CEBAR) Grant (RU006-2017)
Uncontrolled Keywords: breast cancer; drug combination; nuclear factor κB; inflammatory markers; cytokines
Subjects: Q Science > QR Microbiology
R Medicine
S Agriculture > S Agriculture (General)
Divisions: Faculty of Medicine
Faculty of Science > Department of Chemistry
Deputy Vice Chancellor (Research & Innovation) Office > Centre for Research in Biotechnology for Agriculture
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 09 Jan 2020 05:26
Last Modified: 09 Jan 2020 05:26
URI: http://eprints.um.edu.my/id/eprint/23385

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