In Vitro and In Ovo Evaluation of Water-Soluble Extract from Coffea arabica Green Seeds—A Phytotherapeutic Perspective in Cutaneous Oncology ^†

Introduction: Green coffee (Coffea arabica L.), which is rich in phenolic acids, especially chlorogenic acid, has shown favorable effects in metabolic and neurodegenerative disorders [1,2], but data on its antitumor activity on cutaneous melanoma are limited. In the context of the increasing incidence of melanoma and the need for new adjuvant therapeutic options, the present study evaluates the water-soluble fraction of a crude ethanolic extract obtained from green seeds of Coffea arabica, physicochemically characterized [3], regarding the antitumor potential, safety of use on healthy cells, and effects on angiogenesis. Objective: The objective of this study was to investigate the antitumor effect of the water-soluble fraction from Coffea arabica green seeds on human melanoma A375, evaluate its biosafety on normal HaCaT keratinocytes, and analyze its impact on angiogenesis and chorioallantoic irritant potential. Materials and Methods: Water-soluble extract from green seeds of Coffea arabica was tested on human melanoma cell line A375 using the MTT assay [3]. Biosafety evaluation was performed on HaCaT immortalized human keratinocytes using the Alamar Blue assay, analyzing cell viability and morphology. Effects on angiogenesis and irritation were investigated by CAM and HET-CAM assays on the chorioallantoic membrane. Results: The water-soluble fraction (CA-H₂O) obtained from Coffea arabica green seeds showed dose-dependent cytotoxicity on A375 cells, associated with reduced viability, morphological alterations, and increased lactate dehydrogenase (LDH) release, with nuclear aspects indicating apoptosis. In the normal HaCaT cell line, the extract maintained >70% viability at increased concentrations, showing a favorable safety profile. In ovo, the CA-H₂O extract induced significant angiogenesis in the CAM model, without any signs of toxicity or tissue irritation. Conclusions: Based on the results obtained, we can state that the water-soluble fraction (CA-H₂O) can be a promising candidate for dermato-oncological and cosmetic applications, with a favorable balance between antitumor activity, angiogenesis stimulation, and safety profile. The results support further studies to elucidate the molecular mechanisms involved.