Integrated Experimental and Bioinformatic Analysis Reveals Synergistic Apoptotic, Antioxidant, and Immunomodulatory Effects of Hesperidin and Adriamycin in SKOV3 Ovarian Cancer Cells
Aşkın Evren Güler, Mehmet Cudi Tuncer, İlhan Özdemir

TL;DR
This study shows that combining hesperidin and Adriamycin can effectively fight ovarian cancer by boosting apoptosis and antioxidant activity while reducing harmful signaling.
Contribution
The study demonstrates a novel synergistic therapeutic strategy combining hesperidin and Adriamycin for ovarian cancer treatment.
Findings
The combination of hesperidin and Adriamycin showed synergistic cytotoxicity in SKOV3 cells after 48 hours.
Co-treatment upregulated Caspase-3 and Bax while downregulating FOXP3 and EGFR.
Hesperidin significantly enhanced antioxidant capacity in treated cells.
Abstract
Background/Objectives: Ovarian cancer remains one of the most lethal gynecologic malignancies, primarily due to late diagnosis and the development of chemoresistance. Adriamycin (ADR) is effective but limited by systemic toxicity. Natural bioflavonoids such as hesperidin (Hes) may enhance chemotherapy efficacy through oxidative, apoptotic, and immune modulation. This study investigated the antiproliferative, pro-apoptotic, and immunomodulatory effects of Hes and ADR in human ovarian adenocarcinoma cells (SKOV3), focusing on Forkhead box P3 (FOXP3) and epidermal growth factor receptor (EGFR) signaling pathways. Methods: SKOV3 were treated with increasing concentrations of Hes (10–400 µM) and ADR (0.01–0.4 µM), either individually or in combination at their half-maximal inhibitory concentration (IC50) ratios. Cell viability (MTT assay), gene expression (qRT-PCR), cytokine levels (ELISA),…
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Taxonomy
TopicsCancer Mechanisms and Therapy · Bioactive natural compounds · Cytokine Signaling Pathways and Interactions
