Anti-metastatic and anti-tumor effects of the ethyl acetate fraction of Ajwa dates (Phoenix dactylifera L.) in prostate cancer models and its UPLC-based phytochemical profiling.

[ETHNOPHARMACOLOGICAL RELEVANCE] The Al Madina Al Munawwara variety of Phoenix dactylifera L. (Ajwa dates) is a date fruit of cultural, religious, and medicinal significance. Traditionally used in prophetic and alternative medicine, Ajwa dates are reported to possess anti-inflammatory, antioxidant, and anti-cancer properties. However, the role of Ajwa dates in targeting prostate cancer metastasis remains underexplored.

[AIM OF THE STUDY] To evaluate the anti-metastatic and anti-tumor properties of the ethyl acetate fraction of Ajwa dates (EAFAD) against prostate cancer stem-like cells (PC3) in vitro and in vivo, and to identify its bioactive compounds using Ultra-Performance Liquid Chromatography (UPLC).

[MATERIALS AND METHODS] PC3 cells were cultured in ultra-low attachment plates to enrich stem-like cells, confirmed by chemoresistance and toluidine blue staining. EAFAD was evaluated for cytotoxicity (MTT assay), anti-migratory activity (wound-healing, migration, and invasion assays), and anti-tumor efficacy using a xenograft mouse model. UPLC analysis identified bioactive compounds in EAFAD.

[RESULTS] Cancer stem-like cells were enriched, and tumorspheres were formed. EAFAD inhibited the proliferation, migration, and invasive properties of stem-like PC3 cells. The in vivo model showed suppressed tumor growth in the EAFAD-treated group, and histopathological analysis confirmed tumor cell apoptosis. The UPLC analysis of EAFAD confirmed the presence of compounds, including methyl 4-acetoxybenzoate, 2-hydroxycinnamic acid, diosmin, and isorhamnetin-3-O-glucoside, some of which are known for their anticancer and anti-inflammatory activities.

[CONCLUSION] EAFAD exhibited potent in vitro anti-proliferative effects against stem-like PC3 cells. It also demonstrated anti-migratory, anti-invasive effects and notable in vivo anti-tumor activity. These results indicate that EAFAD could serve as a potential therapeutic agent for prostate cancer.