Calcium homeostasis and endoplasmic reticulum stress are involved in Salvianolic acid B-offered protection against cardiac toxicity of arsenic trioxide
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Jing-Yi Zhang1,2,3,4,*, Bin Zhang1,2,3,4,*, Min Wang1,2,3,4, Wei Wang1,2,3,4, Ping Liao5, Gui-Bo Sun1,2,3,4 and Xiao-Bo Sun1,2,3,4
1Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
2Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, China
3Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China
4Zhongguancun Open Laboratory of The Research and Development of Natural Medicine and Health Products, Beijing, China
5College of Pharmacy, Guilin Medical University, Guilin, China
*These authors have contributed equally to this work
Gui-Bo Sun, email: firstname.lastname@example.org
Xiao-Bo Sun, email: email@example.com
Keywords: arsenic trioxide; cardiotoxicity; salvianolic acid B; calcium homeostasis; endoplasmic reticulum stress
Received: January 10, 2017 Accepted: August 26, 2017 Published: October 26, 2017
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 Ca2+ 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 Ca2+ 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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