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

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dc.authoridÖztürk, Şamil / 0000-0002-9435-8139
dc.contributor.authorAlkan Akalin, Senem
dc.contributor.authorAfşin, Yasemin
dc.contributor.authorÖzdemir, İlhan
dc.contributor.authorTuncer, Mehmet Cudi
dc.contributor.authorÖztürk, Şamil
dc.date.accessioned2026-02-03T11:59:52Z
dc.date.available2026-02-03T11:59:52Z
dc.date.issued2025
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractBackground 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-1 beta; IL-6; TNF-alpha); 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-1 alpha 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.
dc.identifier.doi10.3390/medicina61122181
dc.identifier.issn1010-660X
dc.identifier.issn1648-9144
dc.identifier.issue12
dc.identifier.pmid41470183
dc.identifier.scopus2-s2.0-105025959261
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.3390/medicina61122181
dc.identifier.urihttps://hdl.handle.net/20.500.12428/34443
dc.identifier.volume61
dc.identifier.wosWOS:001647035000001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofMedicina-Lithuania
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260130
dc.subjectendometrial cancer
dc.subjectboswellic acid
dc.subjectgemcitabine
dc.subjecthypoxia
dc.subjectangiogenesis
dc.subjectapoptosis
dc.subjectHIF-1 alpha
dc.subjectVEGF
dc.subjectCaspase-3
dc.titleBoswellic Acid Enhances Gemcitabine's Inhibition of Hypoxia-Driven Angiogenesis in Human Endometrial Cancer
dc.typeArticle

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