Oncotarget

Research Papers:

Risk of cancer in patients with heart failure who use digoxin: a 10-year follow-up study and cell-based verification

Min-Huey Chung, Yi-Wen Wang, Yung-Lung Chang, Shih-Ming Huang and Wei-Shiang Lin _

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Oncotarget. 2017; 8:44203-44216. https://doi.org/10.18632/oncotarget.17410

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Abstract

Min-Huey Chung1, Yi-Wen Wang2, Yung-Lung Chang3, Shih-Ming Huang3 and Wei-Shiang Lin4

1Graduate Institute of Nursing, College of Nursing, Taipei Medical University, Taipei 110, Taiwan, Republic of China

2Department of Biology and Anatomy, National Defense Medical Center, Taipei City 114, Taiwan, Republic of China

3Department of Biochemistry, National Defense Medical Center, Taipei City 114, Taiwan, Republic of China

4Department of Medicine, Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei City 114, Taiwan, Republic of China

Correspondence to:

Wei-Shiang Lin, email: [email protected]

Keywords: heart failure, digoxin, cancer, cell-based strategy, personalized medicine

Received: February 18, 2017     Accepted: March 30, 2017     Published: April 25, 2017

ABSTRACT

Heart failure (HF) is the leading cause of death in the world and digoxin remains one of the oldest therapies for HF. However, its safety and efficacy have been controversial since its initial use and there is uncertainty about its long-term efficacy and safety. Recently, the repositioning of cardiac glycosides is to function in anti-tumor activity via multiple working pathways. It is interesting to compare the potential effects of digoxin in clinical patients and cell lines. First, we analyze patient information retrieved from the National Health Insurance Research database of Taiwan between January 1, 2000 and December 31, 2000. This retrospective study included a study cohort (1,219 patients) and a comparison cohort. Our analytical data suggested that patients taking digoxin are at an increased risk of cancers, including breast, liver, and lung cancers, during the 10-year follow-up period. In contrast to the anti-tumor function of digoxin, we further examined the potential pathway of digoxin via the cell-based strategy using several breast cancer cell lines, including MCF-7, BT-474, MAD-MB-231, and ZR-75-1. Digoxin consistently exerted its cytotoxicity to these four cell lines with various range of concentration. However, the proliferation of ZR-75-1 cells was the only cell lines induced by digoxin and the others were dramatically suppressed by digoxin. The responsiveness of SRSF3 to digoxin might be involved with cell-type differences. In summary, we combined a cohort study for digoxin treatment for HF patients with a cell-based strategy that addresses the translation issue, which revealed the complexity of personalized medicine.


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