Efeitos anti-proliferativos e anti-neoplásicos do ácido elágico no melanoma cutâneo: uma revisão integrativa

Abstract

Cutaneous melanoma is a malignant neoplasm originating from melanocytes and represents the leading cause of death among skin cancers due to its high metastatic potential and the resistance of tumor cells to conventional therapies, including chemotherapy, radiotherapy, and immunotherapy with immune checkpoint inhibitors. Plant-derived phenolic compounds have been investigated as promising adjuvants in this context, and ellagic acid (EA) is a natural polyphenol that stands out for its antioxidant, anti-inflammatory, antiproliferative, and pro- apoptotic profile documented across different tumor models. The present work aimed to synthesize the available experimental evidence on the antiproliferative and antineoplastic effects of EA on cutaneous melanoma, with emphasis on the molecular mechanisms identified in preclinical models and on the modulation of the purinergic system as an emerging perspective. Chapter 1 constituted a narrative review of the theoretical background, addressing the epidemiological, histopathological, and molecular aspects of melanoma, the limitations of conventional therapies, and the chemical structure, sources, bioavailability, and general antineoplastic mechanisms of EA across different tumor models, including its inhibitory action on the ectonucleotidases CD39, CD73, and NDPK-B. Chapter 2 configured an integrative literature review, with searches conducted in the PubMed/MEDLINE and SciELO databases, focusing on original experimental studies published between 2015 and 2025 that assessed the effects of EA on cutaneous melanoma models. After screening according to the eligibility criteria and the PRISMA 2020 flowchart, three studies composed the final sample. The findings indicate that EA reduces the viability of murine and human melanoma cell lines (B16, B16F10, A375, and WM115) in a dose- and time-dependent manner, induces G1 cell cycle arrest, promotes apoptosis, and inhibits cell migration and invasion. The molecular mechanisms identified encompass the dual allosteric modulation of PTEN with prolonged inactivation of the PI3K/AKT pathway and accumulation of p53/p21, inhibition of EGFR with reversal of epithelial-mesenchymal transition, and reversible mixed-type inhibition of tyrosinase. Synergism with cisplatin was documented in B16F10 cells, and the clinical relevance of EGFR inhibition was supported by a prognostic correlate in melanoma patients. The data converge toward the recognition of EA as a promising compound for preclinical and translational investigations in the context of cutaneous melanoma, with potential for use in future combined therapeutic strategies.