2. Academic Validation
  3. Fucoidan from Fucus vesiculosus attenuates doxorubicin-induced acute cardiotoxicity by regulating JAK2/STAT3-mediated apoptosis and autophagy

Fucoidan from Fucus vesiculosus attenuates doxorubicin-induced acute cardiotoxicity by regulating JAK2/STAT3-mediated apoptosis and autophagy

  • Biomed Pharmacother. 2020 Oct;130:110534. doi: 10.1016/j.biopha.2020.110534.
Jie Zhang 1,  Zhenzhu Sun 2,  Na Lin 3,  Wenqiang Lu 4,  Xingxiao Huang 4,  Jingfan Weng 4,  Shimin Sun 2,  Chuanjing Zhang 4,  Qi Yang 3,  Guozhong Zhou 5,  Hangyuan Guo 6,  Jufang Chi 7
Affiliations

Affiliations

  • 1 Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, Zhejiang, China; The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
  • 2 The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
  • 3 Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, China.
  • 4 Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, Zhejiang, China.
  • 5 Department of Medical, Shaoxing People's Hospital, Shaoxing, 312000, Zhejiang, China.
  • 6 Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, Zhejiang, China; The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China; Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, China. Electronic address: guohangyuan@zju.edu.cn.
  • 7 Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, 312000, Zhejiang, China; The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China; Zhejiang Chinese Medical University, Hangzhou, 310000, Zhejiang, China. Electronic address: chijufang@zju.edu.cn.
PMID: 32711244 DOI: 10.1016/j.biopha.2020.110534
Abstract

Doxorubicin (DOX) is well-known for its potent antitumor activity but limited by its multiple and serious adverse effects. A major adverse effect is acute cardiotoxicity; yet, its mechanism has not been elucidated. Fucoidan is a multifunctional and nontoxic polysaccharide that is widely studied because of its favorable biological activities and safety. Hence, we proposed that fucoidan may play a protective role in DOX-induced acute cardiotoxicity without causing additional side effects. Sprague-Dawley rats were injected intraperitoneally with a single high dose of DOX to induce acute cardiac injury. Fucoidan was administered orally before DOX injection and AG490, a JAK2 Inhibitor, was applied to verify the participation of the JAK2/STAT3 pathway. In vitro, H9C2 cells were treated with the same drugs at different concentrations and intervention times. in vivo and in vitro results demonstrated that DOX administration induced myocardial damage accompanied by acceleratory Apoptosis and deficient Autophagy in heart tissues or cells, which could be significantly improved by fucoidan supplement. AG490 partly abolished the cardioprotective effects of fucoidan, suggesting the involvement of JAK2 signaling. Additionally, western blotting revealed DOX-induced JAK2/STAT3 pathway activation, which was enhanced by fucoidan and weaken by AG490. Hence, fucoidan exerted a favorable effect on DOX-induced cardiotoxicity by enhancing Autophagy and suppressing Apoptosis in a JAK2/STAT3-dependent manner, which may provide a promising and novel therapeutic strategy against negative chemotherapy-induced effects.

Keywords

Apoptosis and autophagy; Cardiotoxicity; Doxorubicin; Fucoidan; JAK2/STAT3 pathway.

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