Radiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruption
Abstract Gastric cancer is highly lethal due to late-stage diagnosis and resistance to standard treatments like radiotherapy. Enhancing radiosensitivity in gastric cancer cells could improve treatment outcomes. Withaferin A (WA), a bioactive compound from Withania somnifera, has anticancer effects a...
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Nature Portfolio
2025-06-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-05008-x |
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| author | Ping Lu Juan Xue Xuemeng JI |
| author_facet | Ping Lu Juan Xue Xuemeng JI |
| author_sort | Ping Lu |
| collection | DOAJ |
| description | Abstract Gastric cancer is highly lethal due to late-stage diagnosis and resistance to standard treatments like radiotherapy. Enhancing radiosensitivity in gastric cancer cells could improve treatment outcomes. Withaferin A (WA), a bioactive compound from Withania somnifera, has anticancer effects and can modulate cellular processes like autophagy and mitochondrial function. This study investigates WA’s role in enhancing radiosensitivity by targeting apoptosis, autophagy, and mitochondrial function in SGC-7901 gastric cancer cells. In both in vitro and in vivo models, combined WA and radiation (IR) treatment significantly inhibited tumor growth, as evidenced by reduced tumor size in xenografts. Mechanistically, this combination promoted apoptosis, with increased levels of cleaved caspase-3 and PARP, indicating enhanced cell death. WA altered autophagic dynamics by activating autophagy and blocking autophagic flux, shown by LC3II accumulation and SQSTM1/p62 buildup. Moreover, the combined treatment disrupted mitochondrial function, leading to decreased ATP production, reduced respiratory capacity, and increased proton leakage, which contributed to cellular stress. These findings suggest that WA may serve as a radiosensitizer to enhance radiotherapy efficacy in gastric cancer, highlighting its therapeutic potential and advocating for further exploration of phytocompounds in cancer treatment. |
| format | Article |
| id | doaj-art-ecc6ac558be740608a6c82977dd3f0c1 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-ecc6ac558be740608a6c82977dd3f0c12025-08-20T02:30:46ZengNature PortfolioScientific Reports2045-23222025-06-0115111310.1038/s41598-025-05008-xRadiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruptionPing Lu0Juan Xue1Xuemeng JI2Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin Eye Hospital, Nankai University Affiliated Eye Hospital, Nankai University Eye InstituteInstitute of Infection and Immunity, Taihe Hospital, Hubei University of MedicineSchool of Medicine, Nankai UniversityAbstract Gastric cancer is highly lethal due to late-stage diagnosis and resistance to standard treatments like radiotherapy. Enhancing radiosensitivity in gastric cancer cells could improve treatment outcomes. Withaferin A (WA), a bioactive compound from Withania somnifera, has anticancer effects and can modulate cellular processes like autophagy and mitochondrial function. This study investigates WA’s role in enhancing radiosensitivity by targeting apoptosis, autophagy, and mitochondrial function in SGC-7901 gastric cancer cells. In both in vitro and in vivo models, combined WA and radiation (IR) treatment significantly inhibited tumor growth, as evidenced by reduced tumor size in xenografts. Mechanistically, this combination promoted apoptosis, with increased levels of cleaved caspase-3 and PARP, indicating enhanced cell death. WA altered autophagic dynamics by activating autophagy and blocking autophagic flux, shown by LC3II accumulation and SQSTM1/p62 buildup. Moreover, the combined treatment disrupted mitochondrial function, leading to decreased ATP production, reduced respiratory capacity, and increased proton leakage, which contributed to cellular stress. These findings suggest that WA may serve as a radiosensitizer to enhance radiotherapy efficacy in gastric cancer, highlighting its therapeutic potential and advocating for further exploration of phytocompounds in cancer treatment.https://doi.org/10.1038/s41598-025-05008-xWithaferin AAutophagyRadiotherapyGastric cancerRadiosensitizer |
| spellingShingle | Ping Lu Juan Xue Xuemeng JI Radiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruption Scientific Reports Withaferin A Autophagy Radiotherapy Gastric cancer Radiosensitizer |
| title | Radiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruption |
| title_full | Radiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruption |
| title_fullStr | Radiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruption |
| title_full_unstemmed | Radiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruption |
| title_short | Radiosensitizing effects of Withaferin A in gastric cancer cells via autophagy Inhibition and mitochondrial disruption |
| title_sort | radiosensitizing effects of withaferin a in gastric cancer cells via autophagy inhibition and mitochondrial disruption |
| topic | Withaferin A Autophagy Radiotherapy Gastric cancer Radiosensitizer |
| url | https://doi.org/10.1038/s41598-025-05008-x |
| work_keys_str_mv | AT pinglu radiosensitizingeffectsofwithaferinaingastriccancercellsviaautophagyinhibitionandmitochondrialdisruption AT juanxue radiosensitizingeffectsofwithaferinaingastriccancercellsviaautophagyinhibitionandmitochondrialdisruption AT xuemengji radiosensitizingeffectsofwithaferinaingastriccancercellsviaautophagyinhibitionandmitochondrialdisruption |