Evaluation of leucine supplementation on the effects of tumor factors in H9c2 cardiac muscle cells

Author(s)

Maiara Caroline Colombera

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2024-07-10

Examining board members

Maria Cristina Cintra Gomes Marcondes; Helena Cristina de Lima Barbosa; Roger Frigério Castilho

• Advisor: Gabriela de Matuoka e Chiocchetti; Maria Cristina Cintra Gomes Marcondes

Abstract

Cancer cardiac cachexia is a severe and debilitating complication characterised by cardiac dysfunctions associated with tumour progression, but it is often underestimated and poorly studied. Given the difficulties of conducting clinical trials due to the added effects of antineoplastic therapies and constraints in biomolecular and biochemical analyses of patients, it is crucial to conduct experiments in preclinical models. This is essential for gaining a deeper understanding of the mechanisms involved and for developing effective therapeutic strategies. Leucine, an essential branched-chain amino acid, has been shown to play an important role in regulating processes in skeletal muscle wasting in the context of cancer. These processes are often altered in cardiac cachexia, including protein synthesis pathways, mitochondrial activity, proteolysis, and apoptosis. However, the function of leucine in cardiac tissue is still unknown. Therefore, the present study aims to evaluate the effect of tumour progression and leucine on H9c2 cardiac muscle cells, mimicking cardiac cachexia in vitro using two experimental models, with ascitic fluid or serum from cachectic Walker-256-bearing rats. The results revealed a significant decrease in the viability of cardiac muscle cells when exposed to ascitic fluid. Additionally, there was an observed reduction in the expression of complex II of the electron transport chain of oxidative phosphorylation (OXPHOS) in these cells. This suggests mitochondrial dysfunction associated with cardiac cachexia. With regards to leucine treatment, there were no significant changes observed in cell viability, oxygen consumption, or actin and myosin expression, despite the profound alterations produced by exposure to cachectic serum. These findings provide valuable insights into the possible metabolic and mitochondrial alterations underlying cancer cardiac cachexia, emphasizing the necessity for further investigation to improve the targeting of therapeutic interventions (AU)

• FAPESP's process: 20/13222-5 - Evaluation of leucine supplementation on the tumor factors effects in H9c2 cardiac cells
• Grantee: Maiara Caroline Colombera
• Support Opportunities: Scholarships in Brazil - Master