Avaliação do potencial antineoplásico in vitro do PTC+ em células de câncer de pulmão NCI-H460 e NCI-H1975

Abstract

Cancer remains a global health challenge due to their high incidence and mortality rates. Among them, lung cancer stands out as one of the most aggressive types, prompting ongoing discussions about new therapeutic strategies and their underlying biological mechanisms, including antimicrobial, anti-inflammatory, and antineoplastic activities. Despite clinical advances, currently available antineoplastic agents often exhibit significant side effects and may lead to drug resistance in tumor cells. Pterocarpans, the largest class of isoflavonoids, have demonstrated cytotoxic activity against various tumor cell lines, including prostate and breast cancers. This study aimed to evaluate the antiproliferative, cytotoxic, and anti-migratory potential of (+)-2,3,9-trimethoxypterocarpan (PTC+) in non-small cell lung cancer (NSCLC) cell lines (NCI-H460 and NCI-H1975) and non-tumoral lung fibroblasts (MRC-5). Tumor cell lines were cultured at 37 °C in RPMI medium supplemented with 10% fetal bovine serum (FBS) and 1% antibiotic (Pen-Strep, Gibco), while the non-tumoral line was maintained in DMEM. Cell viability was assessed using the MTT assay, revealing that PTC+ exerted time- and concentration-dependent cytotoxic effects, with IC₅₀ values below 3 µM, specifically 1.48 µM for NCI-H460 and 2.91 µM for NCI-H1975 after 72 hours of exposure, presenting more cytotoxic potency in NCI-H460. Morphological analysis using rapid panoptic staining revealed features consistent with apoptosis in NCI-H460 and necrosis in NCI-H1975, particularly at higher compound concentrations. Furthermore, the wound healing assays for cell migration required additional optimization steps to ensure proper standardization and reproducibility of the results. Taken together, the results suggest that (+)-2,3,9-trimethoxypterocarpan exhibits notable cytotoxic activity and induces cell death, potentially through apoptotic or necrotic mechanisms, in lung cancer cell lines, highlighting its promise as a candidate for the development of novel antineoplastic therapeutic strategies.