Journal article
Inhibition of copper transport induces apoptosis in triple-negative breast cancer cells and suppresses tumor angiogenesis
O Karginova, CM Weekley, A Raoul, A Alsayed, T Wu, SSY Lee, C He, OI Olopade
Molecular Cancer Therapeutics | AMER ASSOC CANCER RESEARCH | Published : 2019
Abstract
Treatment of advanced breast cancer remains challenging. Copper and some of the copper-dependent proteins are emerging therapeutic targets because they are essential for cell proliferation and survival, and have been shown to stimulate angiogenesis and metastasis. Here, we show that DCAC50, a recently developed small-molecule inhibitor of the intracellular copper chaperones, ATOX1 and CCS, reduces cell proliferation and elevates oxidative stress, triggering apoptosis in a panel of triple-negative breast cancer (TNBC) cells. Inhibition of ATOX1 activity with DCAC50 disrupts copper homeostasis, leading to increased copper levels, altered spatial copper redistribution, and accumulation of ATP7B..
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Awarded by U.S. Department of Energy
Funding Acknowledgements
Use of the Advanced Photon Source at Argonne National Laboratory was supported by the U.S. Department of Energy, Office of Science, and Office of Basic Energy Sciences, under contract DE-AC02-06CH11357. We thank the U.S. Department of Energy, under contract number DE-FG02-07ER15865 (to C. He), for partial support of this work. We acknowledge funding from Breast Cancer Research Foundation FP049439 (to O.I. Olopade), the National Health and Medical Research Council (Australia; to C.M. Weekley; CJ Martin Overseas Biomedical Fellowship APP1090612), and NIBIB K99 EB022636 (to S.S.-Y. Lee). We thank Dr. Andrei Karginov for helpful comments and assistance with cell imaging, and Dr. Barry Lai for his assistance with XFM imaging.