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Visualization and Quantification of Brown and Beige Adipose Tissues in Mice using [18F]FDG Micro-PET/MR Imaging
Published on: July 1, 2021
Mirabegron displays anticancer effects by globally browning adipose tissues
Xiaoting Sun1,2, Wenhai Sui3, Zepeng Mu4
1Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vison and Brain Health), School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
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.
Insights
Mirabegron, a bladder drug, shows potent anticancer effects by browning adipose tissue. This novel therapeutic approach targets metabolic reprogramming and offers new hope for treating various cancers, including difficult-to-treat types.
Area of Science:
- Oncology
- Metabolic research
- Pharmacology
Background:
- Cancer cells exhibit metabolic reprogramming, relying on glycolysis for growth and metastasis.
- The role of adipose metabolism in tumor progression and therapeutic targeting remains underexplored.
- Targeting metabolic pathways presents a promising avenue for novel cancer therapies.
Purpose of the Study:
- To investigate the potential of targeting adipose metabolism for cancer treatment.
- To evaluate the anticancer efficacy of mirabegron, a drug for overactive bladder.
- To elucidate the mechanism of action of mirabegron in cancer therapy.
Main Methods:
- Utilized various animal cancer models to test mirabegron's efficacy.
- Investigated the role of adipose tissue browning in mediating anticancer effects.
- Examined the impact of genetic deletion of uncoupling protein 1 (UCP1) and removal of brown adipose tissue.
Main Results:
- Mirabegron demonstrated significant anticancer effects across diverse cancer models, including pancreatic and liver cancers.
- The drug's efficacy was directly linked to the browning of adipose tissues.
- Genetic ablation of UCP1 or removal of brown adipose tissue abolished mirabegron's anticancer activity.
Conclusions:
- Mirabegron represents a novel class of anticancer drugs with a unique mechanism of action.
- Targeting adipose tissue browning offers a new therapeutic strategy for multiple cancer types.
- Mirabegron's repurposing holds potential for treating intractable cancers.
