Synergistic Induction of Apoptosis by the Combination of an Axl Inhibitor and Auranofin in Human Breast Cancer Cells

Biomolecules & Therapeutics
Yeon-Sang RyuYoung-Jin Chun

Abstract

Axl receptor tyrosine kinase has been implicated in cancer progression, invasion, and metastasis in various cancer types. Axl overexpression has been observed in many cancers, and selective inhibitors of Axl, including R428, may be promising therapeutic agents for several human cancers, such as breast, lung, and pancreatic cancers. Here, we examined the cell growth inhibition mediated by R428 and auranofin individually as well as in combination in the human breast cancer cell lines MCF-7 and MDAMB- 231 to identify new advanced combination treatments for human breast cancer. Our data showed that combination therapy with R428 and auranofin markedly inhibited cancer cell proliferation. Isobologram analyses of these cells indicated a clear synergism between R428 and auranofin with a combination index value of 0.73. The combination treatment promoted apoptosis as indicated by caspase 3 activation and poly (ADP-ribose) polymerase cleavage. Cancer cell migration was also significantly inhibited by this combination treatment. Moreover, we found that combination therapy significantly increased the expression level of Bax, a mitochondrial proapoptotic factor, but decreased that of the X-linked inhibitor of apoptosis protein. Furthermore,...Continue Reading

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Citations

Mar 2, 2021·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Isao MomoseManabu Kawada
Nov 14, 2020·International Journal of Molecular Sciences·Italia FalconeLudovica Ciuffreda
Aug 18, 2021·The International Journal of Biochemistry & Cell Biology·Lohit Khera, Sima Lev

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Methods Mentioned

BETA
protein assay
transfection
scraping
gene knockdown
flow cytometry
confocal microscopy
nuclear translocation

Software Mentioned

GraphPad Prism
CompuSyn
Quantity One

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