Combined Hesperidin and Doxorubicin Treatment Induces Apoptosis and Modulates Inflammatory Cytokines in HeLa Cervical Cancer Cells
| dc.authorid | 0000-0001-7317-5467 | |
| dc.contributor.author | Ozdemir, Ilhan | |
| dc.contributor.author | Afsin, Yasemin | |
| dc.contributor.author | Tuncer, Mehmet Cudi | |
| dc.contributor.author | Ozturk, Samil | |
| dc.date.accessioned | 2026-02-03T11:59:59Z | |
| dc.date.available | 2026-02-03T11:59:59Z | |
| dc.date.issued | 2025 | |
| dc.department | Çanakkale Onsekiz Mart Üniversitesi | |
| dc.description.abstract | Cervical 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.doi | 10.3390/ijms26178753 | |
| dc.identifier.issn | 1661-6596 | |
| dc.identifier.issn | 1422-0067 | |
| dc.identifier.issue | 17 | |
| dc.identifier.pmid | 40943673 | |
| dc.identifier.scopus | 2-s2.0-105015894799 | |
| dc.identifier.scopusquality | Q1 | |
| dc.identifier.uri | https://doi.org/10.3390/ijms26178753 | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12428/34459 | |
| dc.identifier.volume | 26 | |
| dc.identifier.wos | WOS:001571363300001 | |
| dc.identifier.wosquality | Q1 | |
| dc.indekslendigikaynak | Web of Science | |
| dc.indekslendigikaynak | Scopus | |
| dc.indekslendigikaynak | PubMed | |
| dc.language.iso | en | |
| dc.publisher | Mdpi | |
| dc.relation.ispartof | International Journal of Molecular Sciences | |
| dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | |
| dc.rights | info:eu-repo/semantics/openAccess | |
| dc.snmz | KA_WOS_20260130 | |
| dc.subject | cervical cancer | |
| dc.subject | hesperidin | |
| dc.subject | doxorubicin | |
| dc.subject | apoptosis | |
| dc.subject | cytokines | |
| dc.subject | HeLa cells | |
| dc.subject | RT-qPCR | |
| dc.subject | combination therapy | |
| dc.title | Combined Hesperidin and Doxorubicin Treatment Induces Apoptosis and Modulates Inflammatory Cytokines in HeLa Cervical Cancer Cells | |
| dc.type | Article |











