Abstract
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.
Highlights
Amiodarone is an anti-arrhythmic drug that is widely used to treat the most prevalent type of arrhythmia and atrial fibrillation [1,2,3,4]
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
Our data demonstrated that SRSF3-PTC, the alternative-spliced SFSF3, was observed at the high dose (30 μM) of amiodarone treatment, whereas no alternative splicing p53β form was detected in HeLa cells (Figure 1A)
Summary
Amiodarone is an anti-arrhythmic drug that is widely used to treat the most prevalent type of arrhythmia and atrial fibrillation [1,2,3,4]. It exerts its phamacologcal function through inhibition of diverse ion channels, including sodium, potassium, and calcium channels. Amiodarone alters the function of diverse membrane proteins at therapeutic concentration, resulting in complex therapeutic and toxicity profiles [7, 8]. The detailed mechanism by which amiodarone-induced cancer cell death remains unclear
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