Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Chemosensitizing Effect of Apigenin on T-ALL Cell Therapy(Frontiers Media SA, 2025) Huseynova, N.; Baran, Z.; Khalilov, R.; Mammadova, A.; Baran, Y.T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with limited therapeutic options and frequent treatment-associated toxicities. L-asparaginase, a cornerstone in T-ALL therapy, is often restricted by hypersensitivity reactions and systemic side effects, highlighting the need for safer strategies to enhance its efficacy. This study investigated the potential of apigenin, a naturally occurring flavonoid with antioxidant and pro-apoptotic properties, to act as a chemosensitizer for L-asparaginase in MOLT-4 T-ALL cells. Cytotoxicity was assessed using the MTT assay, apoptosis by Annexin V/PI staining, cell cycle distribution by flow cytometry, and mitochondrial membrane potential by JC-1 staining. Both apigenin and L-asparaginase produced dose- and time-dependent cytotoxicity, with combination treatment resulting in reduced IC<inf>50</inf> values. Apoptotic analysis showed significantly higher apoptosis in the combination-treated groups than in single-agent groups. Cell cycle analysis revealed that apigenin induced S-phase arrest and L-asparaginase induced G1-phase arrest, while the combination disrupted cell cycle progression at multiple checkpoints. JC-1 assay further demonstrated enhanced mitochondrial depolarization, with up to a 29.2-fold increase in cytoplasmic-to-mitochondrial fluorescence ratio in combination therapy compared to L-asparaginase alone. These findings indicate that apigenin potentiates L-asparaginase-induced cytotoxicity through mitochondrial dysfunction and intrinsic apoptotic signaling. The combined use of apigenin and L-asparaginase may provide a novel strategy to improve therapeutic efficacy in T-ALL while potentially reducing the toxicity associated with high-dose L-asparaginase monotherapy. © © 2025 Huseynova, Baran, Khalilov, Mammadova and Baran.Article Citation - Scopus: 2Flavonoids as Chemosensitizers in Leukemias(2025) Huseynova, N.; Çetinkaya, M.; Baran, Z.; Khalilov, R.; Mammadova, A.; Baran, Y.Flavonoids, a diverse group of natural compounds abundant in plants, fruits, and seeds, are not only responsible for the vibrant colors, fragrances, and flavors found in nature but also possess significant health benefits. Representing a secondary metabolite, these phytonutrients contribute to overall well-being. They have garnered considerable interest due to their diverse biological roles, encompassing antioxidant, anti-inflammatory, and anticancer properties. Flavonoids exert anticancer properties by interfering with different signaling pathways and molecules. Also, they have been demonstrated to exert chemosensitization features, where flavonoids may enhance the effectiveness of chemotherapy, and hold promise for improving cancer treatment outcomes as they have been discovered to make cancer cells more responsive to treatment. Understanding their influence on the regulation of cellular signaling provides a foundation for exploring their potential in combination with different chemotherapy agents and their possible single use for cancer treatment. Besides, they are believed to present a cost-effective approach to cancer therapeutics with possible implications for reducing the side effects of the current chemotherapy regimens, which can be a great therapeutic strategy for treating cancer types, including leukemia. This chapter explores potential approaches for creating anticancer treatments, focusing on leukemia, through integrating flavonoid nutraceuticals with traditional chemotherapy agents. © 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.
