Pindolol Mitigates Cancer Cachexia by Modulating Inflammation, Lipolysis, and Muscle Atrophy

Area of Science:

• Biomedical Science
• Oncology
• Pharmacology

Background:

• Cancer cachexia is a debilitating syndrome characterized by inflammation and tissue wasting.
• Current treatments for cancer cachexia are limited, necessitating novel therapeutic approaches.

Purpose of the Study:

• To investigate the therapeutic potential of pindolol in a murine model of cancer cachexia.
• To evaluate pindolol's effects on inflammation, metabolic parameters, and tissue wasting associated with cancer cachexia.

Main Methods:

• In vitro studies assessed B16F10 melanoma cells and pindolol's effect on adipocytes.
• In vivo studies utilized a murine model of cancer cachexia induced by B16F10 melanoma cells, followed by pindolol treatment.
• Assessed body weight, food intake, inflammatory markers, tissue mass, adipokine levels, metabolic markers, and gene expression.

Main Results:

• Pindolol reversed isoproterenol-induced lipolysis in adipocytes in vitro.
• In vivo, pindolol improved body weight, food intake, reduced systemic inflammation, and restored adipokine levels.
• Pindolol preserved skeletal muscle and adipose tissue, improved glucose metabolism and insulin sensitivity, and reduced lipids. It downregulated key muscle atrophy genes (TRIM63, Atrogin-1) and hormone-sensitive lipase (HSL).

Conclusions:

• Pindolol demonstrates significant therapeutic potential in alleviating cancer cachexia.
• Pindolol mitigates cancer cachexia by reducing inflammation, preserving muscle and adipose mass, and improving metabolic function.
• Pindolol represents a promising candidate for future clinical development as a cancer cachexia therapy.