Synergistic Anticancer Effects of Bleomycin and Hesperidin Combination on A549 Non-Small Cell Lung Cancer Cells: Antiproliferative, Apoptotic, Anti-Angiogenic, and Autophagic Insights

• Published in: Pharmaceuticals
• Main Authors: Mehmet Kadir Erdogan, Guleser Ozer
• Format: Article
• Language: English
• Published: MDPI AG 2025-02-01
• Subjects: lung cancer; bleomycin; hesperidin; apoptosis; autophagy; angiogenesis
• Online Access: https://www.mdpi.com/1424-8247/18/2/254

<b>Background</b>: This study investigated the combined effects of hesperidin (Hesp), a natural flavonoid, with bleomycin (BL), a commonly used chemotherapy agent, on A549 human lung cancer cells. <b>Methods</b>: Key parameters assessed included cell viability, colony formation, and cell migration, alongside the expression of apoptotic and autophagic markers (p53, p21, Bax, cleaved PARP, and Beclin-1), VEGF levels, and caspase-3 activity. <b>Results</b>: The findings revealed that the Hesp + BL combination significantly amplified antiproliferative, apoptotic, anti-angiogenic, and autophagic effects compared to either treatment alone. The combination therapy effectively inhibited colony formation and cell migration while markedly reducing VEGF levels, indicating strong anti-angiogenic properties. Apoptotic markers such as p53, p21, Bax, and cPARP were significantly upregulated, with caspase-3 activity confirming robust apoptosis induction. Furthermore, autophagy was notably enhanced, as reflected by increased Beclin-1 expression. <b>Conclusions</b>: Synergistic interactions between Hesp and BL, validated through combination index analysis, underscore the therapeutic potential of this combination. These findings underscore the therapeutic potential of the Hesp + BL combination as a promising strategy for lung cancer treatment, meriting further exploration in diverse lung cancer cell lines to validate and expand its applicability in developing novel therapeutic approaches.