Resveratrol sequentially induces replication and oxidative stresses to drive p53-CXCR2 mediated cellular senescence in cancer cells
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Resveratrol (RSV) acts either as an antioxidant or a pro-oxidant depending on contexts. RSV-treated cancer cells may experience replication stress that can lead to cellular senescence or apoptosis. While both oxidative and replication stresses may mediate the anti-proliferation effect of RSV, to what extent each contributes to the impaired proliferation in response to RSV remains uncharacterized. We here report the study of the roles of replication and oxidative stresses in mediating cellular senescence in cancer cells treated with RSV. RSV induced S-phase arrest and cellular senescence in a dose-dependent manner in U2OS and A549 cancer cells as well as in normal human fibroblasts. We observed that nucleosides significantly alleviated RSV-induced replication stress and DNA damage response, and consequently attenuating cellular senescence. While the elevation of reactive oxygen species (ROS) also mediated the pro-senescent effect of RSV, it occurred after S-phase arrest. However, the induction of ROS by RSV was independent of S-phase arrest and actually reinforced the latter. We also demonstrated a critical role of the p53-CXCR2 axis in mediating RSV-induced senescence. Interestingly, CXCR2 also functioned as a barrier to apoptosis. Together, our results provided more insights into the biology of RSV-induced stress and its cellular consequences.
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Some studies have highlighted RSV's ability to also act as a pro-oxidant molecule, and this dual role depends upon cell type, used dosage, and exposure time.
“Although RSV’s antioxidant properties have been widely demonstrated, some studies [349,350] have highlighted its ability to also act as a pro-oxidant molecule. This dual role depends upon cell type, used dosage, and exposure time [336].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [336]
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Natural substances in cancer—do they work?
Sobolewska, A., Dunisławska, A., & Stadnicka, K. (2021) · Physical Sciences Reviews · doi:10.1515/psr-2019-0060 · Cited by 1 · see citing works
Fruits and Vegetables in Cancer
Vasconcelos, M. D. S., de Oliveira, L. M. N., Nunes-Pinheiro, D. C. S., Viana, C. D. A., Silva, A. F. B., Pinheiro, A. D. N., Santos, S. S., Rocha, J. D. F., Mota, É. F., Jafari, S. M., et al. (2021) · Food bioactive ingredients · doi:10.1007/978-3-030-74035-1_10 · Cited by 1 · see citing works
Erjavec, L. C., Parra, L. G., Sendyk, D. E., Recabarren, M. P., Herbón, C., Favale, N. O., Tulino, S., Carballo, M. A., Nigro, M., Magnani, N., et al. (2025) · BioFactors · doi:10.1002/biof.70018
Paul, B. M., Kannan, G., Arunachalam, K., & Thangaraj, P. (2026) · Inflammopharmacology · doi:10.1007/s10787-026-02346-8
The Relationship Between Immunogenic Cell Death and Cellular Senescence in Cancer Immunotherapy
Shin, S.-A., Kim, M., Kim, M., Choi, S., Park, H. H., & Lee, C. S. (2026) · Life · doi:10.3390/life16091536
- Authors
- Li, B., Hou, D., Guo, H., Zhou, H., Zhang, S., Xu, X., Liu, Q., Zhang, X., Zou, Y., Gong, Y., & Shao, C.
- Affiliations
- Shandong University (CN)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Shao, Changshun
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-03-16
- Volume
- 7
- Issue
- 1
- Pages
- 208-208
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5428242
- OpenAlex
- W2593352862
- Cited by
- 54
- References
- 42
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 5 · 2019: 10 · 2018: 5 · 2017: 3
- FWCI
- 3.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Washington State University
- National Natural Science Foundation of China (81321061, 31371369, 973 Program, 81372241, 81330050, 81572785, 2011CB966200)
- National Key Research and Development Program of China (2011CB966200)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- resveratrol, cellular senescence, replication stress, oxidative stress, p53, CXCR2, reactive oxygen species, S phase arrest, DNA damage response, nucleosides, apoptosis, cancer cells, U2OS cells, A549 cells, normal human fibroblasts
- MeSH terms
- A549 Cells, Resveratrol, Cell Survival, DNA Replication, Dose-Response Relationship, Drug, Humans, Neoplasms, Stilbenes, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Cellular Senescence, Reactive Oxygen Species, Oxidative Stress, Receptors, Interleukin-8B, Cell Line, Tumor, Cell Proliferation, S Phase Cell Cycle Checkpoints
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