Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma

Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma

Abstract 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 an...

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Main Authors: Vitale Del Vecchio, Ibone Rubio Sanchez-Pajares, Sameer Kumar Panda, Ayesha Rehman, Vincenzo De Falco, Aditya Nigam, Laura Mosca, Diana Russo, Claudia Arena, Maria Maddalena Nicoletti, Vincenzo Desiderio, Gianpaolo Papaccio, Luigi Mele, Luigi Laino
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
Xanthohumol
HNSCC
UPR
Cancer stem cells
Endoplasmic reticulum stress
Autophagy
Online Access:https://doi.org/10.1038/s41598-025-98003-1
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Summary:Abstract 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.
ISSN:2045-2322

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