RESUMO
Phytochemical studies are seeking new alternatives to prevent or treat cancer, including different types of leukemias. Campomanesia adamantium, commonly known as guavira or guabiroba, exhibits pharmacological properties including antioxidant, antimicrobial, and antiproliferative activities. Considering the anticancer potential of this plant species, the aim of this study was to evaluate the antileukemic activity and the chemical composition of aqueous extracts from the leaves (AECL) and roots (AECR) of C. adamantium and their possible mechanisms of action. The extracts were analyzed by LC-DAD-MS, and their constituents were identified based on the UV, MS, and MS/MS data. The AECL and AECR showed different chemical compositions, which were identified as main compounds glycosylated flavonols from AECL and ellagic acid and their derivatives from AECR. The cytotoxicity promoted by these extracts were evaluated using human peripheral blood mononuclear cells and Jurkat leukemic cell line. The cell death profile was evaluated using annexin-V-FITC and propidium iodide labeling. Changes in the mitochondrial membrane potential, the activity of caspases, and intracellular calcium levels were assessed. The cell cycle profile was evaluated using propidium iodide. Both extracts caused concentration-dependent cytotoxicity only in Jurkat cells via late apoptosis. This activity was associated with loss of the mitochondrial membrane potential, activation of caspases-9 and -3, changes in intracellular calcium levels, and cell cycle arrest in S-phase. Therefore, the antileukemic activity of the AECL and AECR is mediated by mitochondrial dysfunction and intracellular messengers, which activate the intrinsic apoptotic pathway. Hence, aqueous extracts of the leaves and roots of C. adamantium show therapeutic potential for use in the prevention and treatment of diseases associated the proliferation of tumor cell.
RESUMO
Hancornia speciosa Gomes (Apocynaceae) is a fruit tree, popularly known as mangabeira, and it is widely distributed throughout Brazil. Several parts of the plant are used in folk medicine, and the leaf and bark extracts have anti-inflammatory, antihypertensive, antidiabetic, and antimicrobial properties. In this study, we investigated the chemical composition of the ethanolic extract of Hancornia speciosa leaves (EEHS) and its antioxidant, antimicrobial, and cytotoxic activities as well as the mechanisms involved in cell death. The chemical compounds were identified by liquid chromatography coupled to mass spectrometry (LC-MS/MS). The antioxidant activity of the EEHS was investigated using the method that involves the scavenging of 2,2-diphenyl-1-picrylhydrazyl free radicals as well as the inhibition of oxidative hemolysis and lipid peroxidation induced by 2,2'-azobis (2-amidinopropane) in human erythrocytes. The antimicrobial activity was determined by calculating the minimum inhibitory concentration, minimum bactericidal concentration, minimum fungicidal concentration, and zone of inhibition. Kasumi-1 leukemic cells were used to assess the cytotoxic activity and mechanisms involved in cell death promoted by the EEHS. The chemical compounds identified were quinic acid, chlorogenic acid, catechin, rutin, isoquercitrin, kaempferol-rutinoside, and catechin-pentoside. The EEHS demonstrated antioxidant activity via the sequestration of free radicals, inhibition of hemolysis, and inhibition of lipid peroxidation in human erythrocytes incubated with an oxidizing agent. The antimicrobial activity was observed against American Type Culture Collection (ATCC) and hospital strains of bacteria and fungi, filamentous fungi and dermatophytes. The cytotoxic activity of the EEHS was induced by apoptosis, reduction of the mitochondrial membrane potential, and activation of cathepsins. Together, these results indicate the presence of phenolic compounds and flavonoids in the EEHS and that their antioxidant, antimicrobial, and cytotoxic activities in acute myeloid leukemia cells are mediated by apoptosis.
