Exploring the Immune System’s and Silybin’s Impact on Cancer Cachexia

Author

Patrice Cunningham, University of South CarolinaFollow

Date of Award

8-16-2024

Document Type

Open Access Dissertation

Department

Biomedical Science

First Advisor

Kandy Velazquez

Abstract

Cancer cachexia is a complex syndrome that is characterized by the unintentional loss of body weight with or without fat loss. During cancer cachexia, there is an increase in inflammation consistent with various inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), Interleukin-1 beta (IL-1β ), and interleukin-6 (IL-6); all of which are known to increase proteolysis and aid in the progression of muscle loss and weakness. Immune cells such as macrophages are increased during cachexia and are known to have varying effects on muscle inflammation, regeneration, and the progression of fibrosis in a disease state. However, therapies aimed solely at decreasing inflammatory cytokines have not been successful in reversing skeletal muscle wasting and improving muscle strength during cachexia. Additionally, studies have highlighted a correlation between high platelet count and decreased survival in cachectic patients. Therefore, we hypothesized that platelet count would be increased in cachectic Apc^Min/+ mice and depleting macrophages would ameliorate muscle wasting associated with cancer cachexia. Additionally, we hypothesized that treatment with silybin would improve muscle strength and function in pre-cachectic Apc^Min/+ mice. Mannosylated clodronate liposomes were used to deplete macrophages in the Apc^Min/+ mice and littermate C57bl6 wild-type controls. Treatment with mannosylated clodronate liposomes ameliorated muscle mass loss and improved muscle function in the cachectic Apc^Min/+ mice. Similarly, silybin (a natural compound with anti-inflammatory, anti-fibrotic, and antioxidant properties) improved muscle mass and muscle strength in the pre-cachectic Apc^Min/+ mice. However, we found that platelet levels were increased before the development of cachexia. These findings provide the basis for further investigation of the immunopathogenesis of cancer cachexia. Furthermore, the potential use of natural compound silybin to improve muscle mass and function during cancer cachexia.

Rights

© 2024, Patrice Cunningham

Recommended Citation

Cunningham, P.(2024). Exploring the Immune System’s and Silybin’s Impact on Cancer Cachexia. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/7820