Avaliação dos efeitos dos fungicidas fenpropimorfe e dimetomorfe em células tumorais mamárias e prostáticas

Abstract

Breast cancer and prostate cancer represent major public health challenges in Brazil, with estimated incidences of 78,610 and 77,920 new cases, respectively, for the 2026–2028 triennium. These neoplasms are associated with multiple risk factors, including physical, biological, and chemical agents. Among these, agrochemicals stand out, as they are widely used in agriculture for pest control and to increase productivity. Despite their relevance in the agricultural sector, the potential impacts of these compounds on human health remain incompletely understood, particularly regarding fungicides. In this context, the present study aimed to evaluate the functional and molecular effects of the fungicides Fenpropimorph and Dimethomorph in tumor and non-tumor breast cell lines (MCF-7, MDA-MB-231, and MCF10A) and prostate cell lines (LNCaP, PC-3, and PNT-2), as well as in human fibroblasts (HFF). After the initial viability assay using MTT, the concentrations of 0.125 µM and 0.250 µM of Fenpropimorph were selected for subsequent analyses in the MCF-7 luminal breast cancer cell line after 48 hours of exposure. Dimethomorph showed cytotoxic effect, reducing MTT metabolism at both evaluated time points. The lactate dehydrogenase release assay indicated that Fenpropimorph did not promote significant cytotoxicity at the tested concentrations. However, an increase in Caspase-8 activity, determined by enzymatic assay, was observed, suggesting possible activation of apoptosis-related pathways. In the clonogenic assay, a reduction in the proliferative potential of MCF-7 cells was observed, and treatment with 0.250 µM for 48 hours resulted in increased horizontal migration in the wound healing assay. Finally, quantitative real-time polymerase chain reaction analysis revealed increased expression of Interleukin-1 beta when cells were treated with 0.125 µM of Fenpropimorph. These findings suggest that Fenpropimorph may modulate inflammatory pathways and processes associated with tumor progression in MCF-7 cells. However, additional studies are necessary to further elucidate the molecular mechanisms involved, particularly those related to hormonal signaling pathways