Tags

Type your tag names separated by a space and hit enter

Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells.
J Toxicol Environ Health A. 2019; 82(10):626-637.JT

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 significantly 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.

Authors+Show Affiliations

a College of Pharmacy, Chung-Ang University , Seoul , Korea.a College of Pharmacy, Chung-Ang University , Seoul , Korea.a College of Pharmacy, Chung-Ang University , Seoul , Korea.a College of Pharmacy, Chung-Ang University , Seoul , Korea.a College of Pharmacy, Chung-Ang University , Seoul , Korea.a College of Pharmacy, Chung-Ang University , Seoul , Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31258040

Citation

Ye, Dong-Jin, et al. "Combination Treatment With Auranofin and Nutlin-3a Induces Synergistic Cytotoxicity in Breast Cancer Cells." Journal of Toxicology and Environmental Health. Part A, vol. 82, no. 10, 2019, pp. 626-637.
Ye DJ, Kwon YJ, Baek HS, et al. Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells. J Toxicol Environ Health Part A. 2019;82(10):626-637.
Ye, D. J., Kwon, Y. J., Baek, H. S., Cho, E., Kwon, T. U., & Chun, Y. J. (2019). Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells. Journal of Toxicology and Environmental Health. Part A, 82(10), 626-637. https://doi.org/10.1080/15287394.2019.1635934
Ye DJ, et al. Combination Treatment With Auranofin and Nutlin-3a Induces Synergistic Cytotoxicity in Breast Cancer Cells. J Toxicol Environ Health Part A. 2019;82(10):626-637. PubMed PMID: 31258040.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells. AU - Ye,Dong-Jin, AU - Kwon,Yeo-Jung, AU - Baek,Hyoung-Seok, AU - Cho,Eunah, AU - Kwon,Tae-Uk, AU - Chun,Young-Jin, Y1 - 2019/06/30/ PY - 2019/7/2/pubmed PY - 2020/5/26/medline PY - 2019/7/2/entrez KW - Auranofin KW - breast cancer KW - combination treatment KW - nutlin-3a KW - synergistic effect SP - 626 EP - 637 JF - Journal of toxicology and environmental health. Part A JO - J. Toxicol. Environ. Health Part A VL - 82 IS - 10 N2 - 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 significantly 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. SN - 1528-7394 UR - https://www.unboundmedicine.com/medline/citation/31258040/Combination_treatment_with_auranofin_and_nutlin_3a_induces_synergistic_cytotoxicity_in_breast_cancer_cells_ L2 - http://www.tandfonline.com/doi/full/10.1080/15287394.2019.1635934 DB - PRIME DP - Unbound Medicine ER -