Combined Hesperidin and Doxorubicin Treatment Induces Apoptosis and Modulates Inflammatory Cytokines in HeLa Cervical Cancer Cells

dc.authorid0000-0001-7317-5467
dc.contributor.authorOzdemir, Ilhan
dc.contributor.authorAfsin, Yasemin
dc.contributor.authorTuncer, Mehmet Cudi
dc.contributor.authorOzturk, Samil
dc.date.accessioned2026-02-03T11:59:59Z
dc.date.available2026-02-03T11:59:59Z
dc.date.issued2025
dc.departmentÇanakkale Onsekiz Mart Üniversitesi
dc.description.abstractCervical cancer is a major gynecological malignancy linked to hormonal dysregulation and genetic alterations. Chemotherapy is standard but limited by toxicity and chemoresistance, prompting interest in plant-derived adjuncts. This study examined the anticancer and immunomodulatory effects of Hesperidin (Hes), a citrus flavonoid, with Doxorubicin (DX) in HeLa cervical cancer cells. Cell viability was assessed by MTT assay, apoptotic markers (Bcl-2, Caspase-3) by RT-qPCR, and inflammatory cytokines (IL-1 beta, IL-6, TNF-alpha, IFN-gamma) by ELISA. Cytokine levels were normalized to 10(4) viable cells, and mRNA expression of all four cytokines was quantified by RT-qPCR, confirming protein-level changes and showing the strongest IL-6 suppression with Hes+DX. Chou-Talalay combination index (CI) analysis demonstrated synergistic interactions (CI < 1.0) between Hes and DX across all tested concentrations, with strong synergism (CI < 0.7) at medium and high doses, particularly at 48 and 72 h. Hes alone showed dose-dependent cytotoxicity, while the combination markedly increased Caspase-3, reduced Bcl-2, and decreased IL-1 beta, IL-6, and TNF-alpha, indicating enhanced intrinsic apoptosis and complementary immunomodulation. These results suggest that Hes augments DX's pro-apoptotic and anti-inflammatory effects, potentially allowing lower chemotherapy doses and reduced systemic toxicity in cervical cancer treatment.
dc.identifier.doi10.3390/ijms26178753
dc.identifier.issn1661-6596
dc.identifier.issn1422-0067
dc.identifier.issue17
dc.identifier.pmid40943673
dc.identifier.scopus2-s2.0-105015894799
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.3390/ijms26178753
dc.identifier.urihttps://hdl.handle.net/20.500.12428/34459
dc.identifier.volume26
dc.identifier.wosWOS:001571363300001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherMdpi
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260130
dc.subjectcervical cancer
dc.subjecthesperidin
dc.subjectdoxorubicin
dc.subjectapoptosis
dc.subjectcytokines
dc.subjectHeLa cells
dc.subjectRT-qPCR
dc.subjectcombination therapy
dc.titleCombined Hesperidin and Doxorubicin Treatment Induces Apoptosis and Modulates Inflammatory Cytokines in HeLa Cervical Cancer Cells
dc.typeArticle

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