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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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-98003-1 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Vitale Del Vecchio |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6098369692b249a59c1be4e4d3b8f78f |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-6098369692b249a59c1be4e4d3b8f78f2025-08-20T02:17:57ZengNature PortfolioScientific Reports2045-23222025-04-0115111310.1038/s41598-025-98003-1Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinomaVitale Del Vecchio0Ibone Rubio Sanchez-Pajares1Sameer Kumar Panda2Ayesha Rehman3Vincenzo De Falco4Aditya Nigam5Laura Mosca6Diana Russo7Claudia Arena8Maria Maddalena Nicoletti9Vincenzo Desiderio10Gianpaolo Papaccio11Luigi Mele12Luigi Laino13Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Life Sciences, Health and Health Professions, Link Campus UniversityMultidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”Multidisciplinary Department of Medical-Surgical and Dental Specialties, University of Campania “L. Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Health Sciences, University of BasilicataDermatology Unit, University of Campania “L.Vanvitelli”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.https://doi.org/10.1038/s41598-025-98003-1XanthohumolHNSCCUPRCancer stem cellsEndoplasmic reticulum stressAutophagy |
| spellingShingle | 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 Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma Scientific Reports Xanthohumol HNSCC UPR Cancer stem cells Endoplasmic reticulum stress Autophagy |
| title | Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma |
| title_full | Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma |
| title_fullStr | Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma |
| title_full_unstemmed | Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma |
| title_short | Xanthohumol modulate autophagy and ER stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma |
| title_sort | xanthohumol modulate autophagy and er stress to counteract stemness and enhance cisplatin efficacy in head and neck squamous cell carcinoma |
| topic | Xanthohumol HNSCC UPR Cancer stem cells Endoplasmic reticulum stress Autophagy |
| url | https://doi.org/10.1038/s41598-025-98003-1 |
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