Potencial antitumoral do extrato da casca de Geissospermum vellosii em câncer de mama: estudo in vitro da atividade citotóxica, anti migratória e antiproliferativa

Abstract

Introduction: Breast cancer is the most common cancer among women worldwide, and resistance to chemotherapeutic agents represents a major challenge to therapeutic success. In this context, secondary metabolites from plant species emerge as promising sources for the development of new drugs. Geissospermum vellosii (Apocynaceae), popularly known as Pau-Pereira (PP), is a species rich in indole alkaloids with antioxidant and antitumor activities, but with no previous studies in different human breast cancer cell lines. Objectives: This study evaluated the in vitro antitumor effect of the ethanolic extract from the stem bark of PP in human breast cancer cell lines. Methodology: The human breast cancer cell lines MCF-7

(hormone receptor–positive) and MDA-MB-231 (hormone receptor–negative, triple- negative), as well as the non-tumorigenic human mammary cell line MCF-10, were

used as controls. Cell viability, half-maximal inhibitory concentration (IC5 0 ), and selectivity index (SI) were determined after 24, 48, and 72 hours of treatment with PP extract at concentrations ranging from 5 to 100 μg/mL using the MTT colorimetric assay. Morphological aspects were analyzed by optical microscopy. Proliferative capacity was evaluated by the colony formation assay. Cell migration was assessed using the scratch assay. Finally, the pro-apoptotic effect was evaluated by flow cytometry and fluorescence microscopy, with cell cycle analysis using propidium iodide staining. Results: The extract reduced cell viability in a time- and concentration-dependent manner. The IC5 0 values for MCF-7 and MDA-MB-231 at 48 h were 19.75 μg/mL and 18.60 μg/mL, respectively. However, MCF-10 showed the lowest IC5 0 (2.74 μg/mL), suggesting low selectivity toward the control cell line. Morphological analysis indicated cellular alterations suggestive of apoptosis after treatment. In the colony formation assay, the extract showed inhibitory effects in all cell lines. In the scratch assay, reduced cell migration was observed after 48 hours in a concentration-dependent manner, with a more pronounced effect at 24 h in the MDA-MB-231 cell line. The evaluation of the pro-apoptotic effect demonstrated that the extract induced apoptosis in a concentration-dependent manner, possibly through cell cycle arrest at G1 in all cell lines. Conclusion: The stem bark extract of G. vellosii showed antitumor potential based on its antiproliferative, antimigratory, and pro-apoptotic effects in breast cell lines, confirming its potential as a source of prototype drugs for chemotherapy.