Amiodarone promotes cancer cell death through elevated truncated SRSF3 and downregulation of miR-224
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Yung-Lung Chang1, Shu-Ting Liu1, Yi-Wen Wang2, Wei-Shiang Lin3 and Shih-Ming Huang1
1Department of Biochemistry, National Defense Medical Center, Taipei City, Taiwan 114, Republic of China
2Department of Biology and Anatomy, National Defense Medical Center, Taipei City, Taiwan 114, Republic of China
3Division of Cardiology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei City, Taiwan 114, Republic of China
Wei-Shiang Lin, email: firstname.lastname@example.org
Shih-Ming Huang, email: email@example.com
Keywords: amiodarone; digoxin; caffeine; autophagy; miR-224
Received: July 10, 2017 Accepted: January 13, 2018 Published: February 03, 2018
Amiodarone is a widely used class III antiarrhythmic agent which prolongs the action potential and refractory period by blockage of several types of myocardial potassium channels. Emerging evidence suggests that amiodarone sensitize tumor cells in response to chemotherapy. Nevertheless, little is known about the underlying molecular mechanism. To gain further insight, we demonstrated that amiodarone accumulated the population of a premature termination codon-containing isoform of serine and arginine rich splicing factor 3 (SRSF3-PTC) without increasing alternative spliced p53 beta isoform. Amiodarone enhanced reactive oxygen species production and increased cell apoptosis, whereas reduced DNA damage. Moreover, amiodarone suppressed miR-224 and increased its target COX-2 expression. Taken together, our results suggested amiodarone caused cancer cell death might be through increased SRSF3-PTC and miR-224 reduction in a p53-independent manner.
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