Boswellic Acid Enhances Gemcitabine's Inhibition of Hypoxia-Driven Angiogenesis in Human Endometrial Cancer.

Background and

Objectives

Endometrial carcinoma is among the most common gynecological malignancies, with recurrence and chemoresistance remaining major clinical challenges. This study aimed to evaluate the combined effects of Boswellic acid (BA), a natural pentacyclic triterpene, and Gemcitabine (GEM), a nucleoside analog chemotherapeutic, on hypoxia, angiogenesis, and apoptosis in human endometrial cancer cells. Materials and

Methods

ECC-1 cells were treated with BA, GEM, or their combination under normoxic and hypoxic conditions. Cell viability (MTT assay); nuclear morphology (NucBlue staining); cell cycle distribution (PI flow cytometry); angiogenesis (VEGF ELISA expression); apoptosis (Caspase-3/7 activity; Bax; Bcl-2 expression); inflammatory cytokines (IL-1β; IL-6; TNF-α); and gene ontology enrichment were analyzed.

Results

Both BA and GEM reduced cell viability in a dose- and time-dependent manner, with the combination producing synergistic cytotoxicity and lower IC50 values. Hypoxia enhanced drug sensitivity, particularly in combination therapy. BA and GEM significantly suppressed HIF-1α and VEGF expression, with maximal inhibition observed in the combination group. Apoptotic induction was confirmed by increased Bax and Caspase-3 and decreased Bcl-2 expression, together with elevated Caspase-3/7, -8, and -9 activity. Pro-inflammatory cytokine levels were markedly reduced, and gene ontology analysis revealed enrichment of apoptotic, anti-proliferative, and anti-angiogenic pathways.

Conclusions

BA + GEM combination synergistically suppresses hypoxia-driven angiogenesis and promotes apoptosis in endometrial cancer cells. These findings support its potential as an adjuvant therapeutic approach, warranting further preclinical and clinical validation.