Chemical Characterization and Evaluation of the Antitumoral Activity of Annona tomentosa R.E.Fr. on Breast (MCF-7) Three-Dimensional (3D) Tumor Spheroids

Annona tomentosa, popularly known as “araticum marolo”, is an Annonaceae with little scientific evidence regarding its phytochemistry and biological activities. Based on this, the present study carried out the chemical characterization of the methanolic extract and fractions of ethyl acetate and alkaloid of the stem bark of A. tomentosa, in addition to evaluating their influence on the viability, proliferation and migration of breast (MCF-7) cells in a three-dimensional (3D) model. The samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the Global Natural Products Social Networking (GNPS) platform was used to construct a molecular network. 21 compounds were identified, of which 16 belong to the alkaloid class. Multicellular spheroids (MCTS) growth was reduced after 216 h of treatment, as well as their viability (ca. 50% for the extract and ca. 25% for the alkaloid fraction). The extract and the alkaloid fraction showed greater antiproliferative (at a concentration of 100 µg mL-1 after 216 h, ca. 48% for the extract and ca. 20% for the fraction) and antimigratory (at concentrations 50-500 µg mL-1 for the extract and 100-250 µg mL-1 for the fraction) effects. This study is pioneering in demonstrating the antitumor effects in a 3D culture model, also revealing its potential for the isolation of alkaloids.