Dihydroartemisinin ameliorates skeletal muscle atrophy in the lung cancer cachexia mouse model

J Cancer Res Ther. 2024 Dec 1;20(7):2004-2012. doi: 10.4103/jcrt.jcrt_140_24. Epub 2025 Jan 10.

Abstract

Introduction: Cancer cachexia (CC) is characterized by weight loss with specifically reduced skeletal muscles and adipose tissues in patients with late-stage cancer. Dihydroartemisinin (DHA), an effective antimalarial derivative of artemisinin, has been demonstrated to have anti-inflammatory and antitumor properties.

Materials and methods: This study examined the effects of DHA on the Lewis lung carcinoma (LLC)-induced CC mouse model.

Results: DHA treatment significantly increases tumor-free body weight and food intake but decreases serum interleukin-6 level and tumor weight in CC mice. In addition, DHA treatment relieves muscle atrophy and decreases muscle ring finger 1 (MuRF1) and F-box-only protein 32 (Fbx32) expressions in CC mice. In vitro, DHA reverses the reduction in myotube formation induced by an LLC-conditioned medium and increases Fbx32 expression in C2C12 mouse myotubular cells.

Conclusions: Our study demonstrated that DHA ameliorates the cachectic state and skeletal muscle atrophy in LLC-induced cachectic mouse models, suggesting its therapeutic potential for CC.