Mirabegron displays anticancer effects by globally browning adipose tissues

Xiaoting Sun, Wenhai Sui, Zepeng Mu, Sisi Xie, Jinxiu Deng, Sen Li, Takahiro Seki, Jieyu Wu, Xu Jing, Xingkang He, Yangang Wang, Xiaokun Li, Yunlong Yang (), Ping Huang (), Minghua Ge () and Yihai Cao ()
Additional contact information
Xiaoting Sun: Wenzhou Medical University
Wenhai Sui: Qilu Hospital of Shandong University
Zepeng Mu: Affiliated Hospital of Medical College Qingdao University
Sisi Xie: Fudan University
Jinxiu Deng: Fudan University
Sen Li: Fudan University
Takahiro Seki: Tumor and Cell Biology, Karolinska Institutet
Jieyu Wu: Tumor and Cell Biology, Karolinska Institutet
Xu Jing: Tumor and Cell Biology, Karolinska Institutet
Xingkang He: Zhejiang University Medical School
Yangang Wang: Affiliated Hospital of Medical College Qingdao University
Xiaokun Li: Wenzhou Medical University
Yunlong Yang: Fudan University
Ping Huang: Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College
Minghua Ge: Center of Otolaryngology-Head and Neck Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College
Yihai Cao: Tumor and Cell Biology, Karolinska Institutet

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Metabolic reprogramming in malignant cells is a hallmark of cancer that relies on augmented glycolytic metabolism to support their growth, invasion, and metastasis. However, the impact of global adipose metabolism on tumor growth and the drug development by targeting adipose metabolism remain largely unexplored. Here we show that a therapeutic paradigm of drugs is effective for treating various cancer types by browning adipose tissues. Mirabegron, a clinically available drug for overactive bladders, displays potent anticancer effects in various animal cancer models, including untreatable cancers such as pancreatic ductal adenocarcinoma and hepatocellular carcinoma, via the browning of adipose tissues. Genetic deletion of the uncoupling protein 1, a key thermogenic protein in adipose tissues, ablates the anticancer effect. Similarly, the removal of brown adipose tissue, which is responsible for non-shivering thermogenesis, attenuates the anticancer activity of mirabegron. These findings demonstrate that mirabegron represents a paradigm of anticancer drugs with a distinct mechanism for the effective treatment of multiple cancers.

Date: 2023
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DOI: 10.1038/s41467-023-43350-8

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