Time-Resolved Metabolomics Reveals Distinct, Cell- and Variety-Dependent Profiles of Prostanoids in Melanoma Cells Exposed to Fruit Extracts from Cornus mas and C. officinalis: A Pilot Study

Chronic inflammation and cyclooxygenase (COX)-2–mediated prostanoid signaling contribute to melanoma progression, yet their modulation by natural products remains poorly defined. We examined the effects of dogwood fruit extracts—Japanese cornel (Cornus officinalis) and two European cultivars (‘Uholok’, ‘Yantarnyi’)—on temporal prostanoid dynamics in A375 (primary tumor–derived) and MeWo (metastasis-derived) mela-noma cells. Dynamic changes rather than static levels were modeled using GAMLSS or zero-inflated Gamma models to assess time, cell line, cornel type, and dose effects. Untreated A375 cells showed time-dependent increases in PGE2, PGF2α, thromboxane B2, and 13,14-dihydro-PGE1, consistent with inducible COX-2 activation, whereas MeWo cells maintained consistently high prostanoid levels, reflecting constitutive COX-2 expression. Cornus extracts modulated these trajectories in a cell- and dose-dependent manner. In A375, low concentrations allowed prostanoid accumulation, while higher doses flattened or reversed these increases; Japanese cornel produced the strongest inhibition, whereas European cultivars showed weaker or cultivar-specific effects. MeWo cells were less responsive, with significant changes emerging only at higher doses. PGD2 and 6-keto-PGF1α remained largely unchanged, indicating selective targeting of COX-2–dependent prostanoids. Extracts also reduced accumulation of downstream prostanoids, including 15-deoxy-Δ12,14-PGJ2 and 13,14-dihydro-PGE1, particularly in A375 cells. These differences highlight a stronger susceptibility of early-stage melanoma to phytochemical intervention and support cultivar-dependent bioactivity linked to phytochemical composition. In summary, Cornus extracts selectively attenuate time-dependent trajectories of tumor-promoting prostanoids—most effectively with Japanese cornel—while sparing homeostatic mediators, warranting further investigation on their potential for melanoma chemoprevention or adjunctive therapy.