Del Vecchio Vitale, Sanchez-Pajares Ibone Rubio, Panda Sameer Kumar, Rehman Ayesha, De Falco Vincenzo, Nigam Aditya, Mosca Laura, Russo Diana, Arena Claudia, Nicoletti Maria Maddalena, Desiderio Vincenzo, Papaccio Gianpaolo, Mele Luigi, Laino Luigi
Department of Experimental Medicine, University of Campania "Luigi Vanvitelli", Naples, 80138, Italy.
Department of Life Sciences, Health and Health Professions, Link Campus University, Via del Casale di San Pio V 4, Roma, 00165, Italia.
Sci Rep. 2025 Apr 16;15(1):13137. doi: 10.1038/s41598-025-98003-1.
Natural compounds have been increasingly investigated for their efficient anti-cancer activity. Xanthohumol (XN), a flavonoid derived from hops, has shown promise in preclinical studies for various cancers due to its unique biological properties. This study investigates the effects of XN and a cost-effective hop extract (HOP EX) on head and neck squamous cell carcinoma (HNSCC), focusing on their potential to modulate cancer stemness and enhance the efficacy of Cisplatin chemotherapy. Using a combination of flow cytometry, qPCR, and cellular assays, we assessed the impact of XN and HOP EX on cell viability, stemness, and chemoresistance in HNSCC cell lines. Further, we explored the underlying mechanisms by examining the induction of apoptosis, ER stress, and autophagy activation. Our findings demonstrate that both XN and HOP EX significantly decrease cell viability and stemness in HNSCC cells and enhance the cytotoxic effects of Cisplatin, suggesting a synergistic interaction. Mechanistically, we identified that the induction of ER stress and subsequent activation of the unfolded protein response (UPR) promote autophagy, leading to increased apoptosis. By modulating key cellular pathways such as ER stress and autophagy, these natural compounds could be developed into supportive treatments for HNSCC.
天然化合物因其高效的抗癌活性而受到越来越多的研究。黄腐酚（XN）是一种从啤酒花中提取的黄酮类化合物，由于其独特的生物学特性，在多种癌症的临床前研究中显示出前景。本研究调查了XN和一种经济高效的啤酒花提取物（HOP EX）对头颈部鳞状细胞癌（HNSCC）的影响，重点关注它们调节癌症干性和增强顺铂化疗疗效的潜力。通过流式细胞术、qPCR和细胞试验相结合的方法，我们评估了XN和HOP EX对HNSCC细胞系的细胞活力、干性和化疗耐药性的影响。此外，我们通过检测细胞凋亡、内质网应激和自噬激活的诱导情况，探索了其潜在机制。我们的研究结果表明，XN和HOP EX均能显著降低HNSCC细胞的活力和干性，并增强顺铂的细胞毒性作用，提示存在协同相互作用。从机制上讲，我们发现内质网应激的诱导以及随后未折叠蛋白反应（UPR）的激活促进了自噬，导致细胞凋亡增加。通过调节内质网应激和自噬等关键细胞途径，这些天然化合物可被开发为HNSCC的辅助治疗方法。
