Journal
ONCOTARGET
Volume 8, Issue 57, Pages 97384-97393Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.22127
Keywords
arsenic trioxide; cardiotoxicity; salvianolic acid B; calcium homeostasis; endoplasmic reticulum stress
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Funding
- Special Project for the National Traditional Chinese Medicine Industry of China [201507004]
- National Natural Science Foundation of China [81374011]
- Major Scientific and Technological Special Project for Significant New Drugs Formulation [2017ZX09301069]
- PUMC Youth Fund [3332015049]
- Fundamental Research Funds for the Central Universities
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Arsenic trioxide (ATO) is a potent anticancer agent used to treat acute promyelocytic leukemia. However, its cardiotoxicity limits ATO's widespread clinical use. Previous studies demonstrated that ATO may aggravate Ca2+ overload and promote endoplasmic reticulum stress (ERS). Salvianolic acid B (Sal B) is cardioprotective against ATO and enhances ATO's anticancer activities. The present study assessed whether the Sal B protective effect was related to maintenance of Ca(2+ )homeostasis and inhibition of ER stress. Male BALB/c mice were injected with ATO or ATO+Sal B once a day via the tail vein for 2 weeks. We then detected the effects of Sal B in real time using adult rat ventricular cardiomyocytes in vitro using an IonOptix MyoCam system. Sal B treatment alleviated ATO-induced abnormal cardiac contractions and Ca(2+ )homeostasis imbalance. Sal B increased sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity, regulated Ca2+ handling protein expression, and decreased expression of ERS proteins. Our results demonstrate that the cardioprotective effect of Sal B correlates with SERCA modulation, maintenance of Ca2+ homeostasis, and inhibition of ER stress. These findings suggest Sal B may ameliorate ATO cardiotoxicity during clinical application.
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