Effect of the exercise mimetic AICAR on BACH1 mRNA levels in colon cancer cell line (CT26)

• Grant number: 24/02597-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2024
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Physical Education
• Principal Investigator: Patricia Chakur Brum
• Grantee: Sabrina Meiriane da Silva Cruz
• Host Institution: Escola de Educação Física e Esporte (EEFE). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cancer encompasses a group of diseases originating from genetic mutations within cells, leading to uncontrolled cell division and the ability to invade surrounding tissues. According to the Global Cancer Observatory, colon cancer ranks as the third most incident type of cancer worldwide. In Brazil, it stands as the third most fatal cancer. While conventional pharmacological treatments remain the primary option for addressing colon cancer, there is a growing interest within the scientific community in exploring complementary therapies. Physical exercise has gained attention due to its potential impact on cancer prevention, progression, and remission. Consequently, it has been extensively adopted as a complementary therapy. Previous data from our laboratory, using an animal model, demonstrated that exercise training could decrease BACH1 mRNA levels in mice with colon cancer (CT26). BACH1, a transcription factor, plays a crucial role in regulating the cell cycle, apoptosis, and lipid metabolism, with close associations to various tumor types. In fact, literature data indicate that an upregulation of the BACH1 gene or protein is linked to the metastatic capacity of cancer cells, migration, invasion, and metastasis properties in both in vivo and in vitro models, underscoring its pro-tumor effects. The objective of the current study is to assess the impact of physical exercise on the BACH1 transcription factor mRNA levels in a colon cancer cell line (CT26). To achieve this, we will use AICAR, known as an AMPK activator, which is considered a mimetic of physical exercise. AICAR has been extensively studied for its ability to inhibit the growth and survival of cancer cells. Therefore, this project aims to evaluate the influence of pharmacologically induced alterations in the expression of BACH1, using cobalt protoporphyrin to increase expression and hemin to inhibit it. We will assess various parameters, including viability, cytotoxicity, migration, and invasion of CT26 tumor cells, providing valuable insights into the potential role of exercise and associated pharmacological interventions in colon cancer treatment. (AU)