Cancer cachexia is a complex syndrome associated with chronic inflammation, catabolic dysregulation, and sympathetic nervous system hyperactivity contribute to energy imbalance and skeletal muscle and adipose tissue wasting. This study investigates the therapeutic potential of pindolol in a murine model of cancer cachexia. In vitro study evaluated the cachexia-inducing potential of B16F10 melanoma cells and the therapeutic effects of pindolol on 3T3-L1 adipocytes. In vivo, cachexia was induced in male C57BL/6 mice via subcutaneous B16F10 melanoma cell injection, followed by pindolol treatment until the tumor volume reached 5000 mm³. Body weight, food intake, inflammatory markers, muscle and adipose tissue mass, adipokine levels, metabolic markers, organ weights, and gene expression of E3 ubiquitin-protein ligase TRIM63, Muscle Atrophy F-box gene (atrogin-1), and hormone sensitive lipase (HSL) were assessed. B16F10-conditioned media along with isoproterenol induced lipolysis in 3T3-L1 adipocytes, while pindolol reversed this effect. In vivo, pindolol significantly improved body weight, food intake, and systemic inflammation while restoring adipokine levels. Pindolol also preserved skeletal muscle and adipose depots, improved glucose levels, enhanced insulin sensitivity, and lowered triglycerides and cholesterol. Histological analysis confirmed muscle and adipose tissue preservation. Pindolol downregulated TRIM63 and Atrogin-1, reducing muscle atrophy, and decreased HSL, suggesting reduced lipolysis evident from mRNA expression. Pindolol alleviates cancer cachexia by reducing inflammation, preserving muscle and adipose mass, and improving metabolic parameters, highlighting its potential as a therapeutic candidate.
Joshi et al. (Mon,) studied this question.
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