Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells
- Authors
- Ye, Dong-Jin; Kwon, Yeo-Jung; Baek, Hyoung-Seok; Cho, Eunah; Kwon, Tae-Uk; Chun, Young-Jin
- Issue Date
- May-2019
- Publisher
- TAYLOR & FRANCIS INC
- Keywords
- Auranofin; nutlin-3a; synergistic effect; combination treatment; breast cancer
- Citation
- JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v.82, no.10, pp 626 - 637
- Pages
- 12
- Journal Title
- JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES
- Volume
- 82
- Number
- 10
- Start Page
- 626
- End Page
- 637
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/32828
- DOI
- 10.1080/15287394.2019.1635934
- ISSN
- 1528-7394
1087-2620
- Abstract
- Auranofin is a gold complex categorized as an anti-rheumatic agent. Recently, several investigators suggested that auranofin may act as a potent anti-cancer drug for breast tumors. Nutlin-3a is a cis-imidazoline analog which prevents interaction between mouse double minute 2 homolog (MDM2) and the tumor suppressor p53. The aim of this study was to examine cell growth inhibition mediated by auranofin or nutlin-3a individually as well as in combination with MCF-7 and MDA-MB-231 cells. To assess any potential synergistic effects between auranofin and nutlin-3a, low concentrations of auranofin and nutlin-3a were simultaneously incubated with MCF-7 and MDA-MB-231 cells. Cell viability assay, caspase-3/7 assay, and poly (ADP-ribose) polymerase cleavage revealed that auranofin and nutlin-3a exerted a synergistic effect on cancer cell apoptosis. Isobologram analysis of MCF-7 and MDA-MB-231 cells noted evident synergism between auranofin and nutlin-3a. The combined treatment increased the expression of mitochondrial pro-apoptotic factors such as Bcl-2 associated X protein and Bcl-2 homologous antagonist/killer. Further, combination treatment signi?cantly enhanced reactive oxygen species (ROS) generation in MCF-7 and MDA-MB-231 cells. In conclusion, data demonstrated that combined treatment with auranofin and nutlin-3a exhibited a synergistic action on breast cancer cells and this combination may be considered for use as a novel therapeutic strategy for breast cancer.
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Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
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