Avaliação da atividade anticancerígena e imunomoduladora de derivados bioativos terpênicos

Abstract

Introduction: Cancer is a disease that affects millions of people around the world, being one of the main causes of death and a significant barrier to life expectancy. Despite therapeutic advances, toxicity and therapeutic resistance still represent a major challenge in cancer treatment. Natural products, especially special metabolites found in many medicinal plants, have great therapeutic potential due to their diverse biological characteristics. For example, the genus Copaifera has several pharmacological activities, including anticancer, but it is still very little studied. Objective: this study aimed to evaluate the anticancer and immunomodulatory properties of natural terpene compounds obtained from Copaifera oleoresin. Material and Methods: the compounds were obtained through flash chromatography using 70-230 mesh silica gel impregnated with potassium hydroxide. The cell lines HL-60 (Acute Myeloid Leukemia), K562 (Chronic Myeloid Leukemia), as well as PBMC cells (Normal Peripheral Blood Mononuclear Cells), Vero (Cercopithecus aethiops mouthwash epithelial cell) and neutrophils were used. The Methylthiazoltrazolium (MTT) cell prediction test was used to estimate the cytotoxicity of the compounds. To evaluate immunomodulation, assays were carried out on the production of ROS (reactive oxygen species), NETs (neutrophil extracellular traps) and measurement of cytokines (IL-1β, IL-6, IL-8 and IL-10) in neutrophils. Results and conclusion: The copalic and polyaltic acid compounds exhibited IC50 values of 19.36 and 26.54 μg/mL against strains K562 and HL60, respectively. The compounds 3-acetoxy-copalic acid and 3-hydroxy-copalic acid exhibited values of 13.73 and 33.20 μg/mL, respectively, against strain K562. Our results revealed that diterpene compounds isolated from oleoresin from Copaifera spp present cytotoxic activity in neoplastic cells, but present dose-dependent toxicity in normal cells. Specifically, 3-hydroxy-copalic acid showed significant toxicity in K562 and HL60 neoplastic cells, with minimal effects on normal cells, highlighting its potential as a cancer therapeutic agent. Therefore, the compounds 3-acetoxy-copalic and 3-hydroxy-copalic acids were selected to evaluate their immunomodulatory potential. The results indicate that these compounds support neutrophil probability while increasing the release of ROS and NETs. They also elevate histone release and modulate cytokine levels. These findings highlight the complex immunomodulatory effects of the compounds, highlighting the need for further elucidation of mechanisms and methodological references in future studies.