Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels
Abstract
Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Aberrant Nrf2 expression and poor prognosis have been revealed in a wide range of cancers, including lung, esophageal, breast, bladder, liver, prostate, and colorectal carcinomas.
“numerous studies have revealed aberrant Nrf2 expression and poor prognosis in a wide range of cancers, including, among others, lung, esophageal, breast, bladder, liver, prostate, and colorectal carcinomas [161,162,169,170,171,173,174]”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [174]
Cites
Jemal, A., Tiwari, R. C., Murray, T., Ghafoor, A., Samuels, A., Ward, E., Feuer, E. J., & Thun, M. J. (2004) · CA: A Cancer Journal for Clinicians · doi:10.3322/canjclin.54.1.8 · Cited by 3,984 · see citing works
Bolla, M., Collette, L., Blank, L., Warde, P., Dubois, J. B., Mirimanoff, R.-O., Storme, G., Bernier, J., Kuten, A., Sternberg, C., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09408-4 · Cited by 1,686 · see citing works
Androgen Deprivation Therapy for Prostate Cancer
Sharifi, N. (2005) · JAMA · doi:10.1001/jama.294.2.238 · Cited by 1,087 · see citing works
Itoh, K., Tong, K. I., & Yamamoto, M. P. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.02.075 · Cited by 866 · see citing works
Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention
Cheung, K. L., & Kong, A. T. (2009) · The AAPS Journal · doi:10.1208/s12248-009-9162-8 · Cited by 365 · see citing works
Chen, Y., Clegg, N. J., & Scher, H. I. (2009) · The Lancet Oncology · doi:10.1016/s1470-2045(09)70229-3 · Cited by 322 · see citing works
Prooxidant-Antioxidant Shift Induced by Androgen Treatment of Human Prostate Carcinoma Cells
Ripple, M. O., Wilding, G., Henry, W. F., & Rago, R. P. (1997) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/89.1.40 · Cited by 309 · see citing works
Chemoprevention by isothiocyanates and their underlying molecular signaling mechanisms
Keum, Y., Jeong, W., & Kong, A. (2004) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.05.024 · Cited by 281 · see citing works
The role of Nrf2 in increased reactive oxygen species and DNA damage in prostate tumorigenesis
Frohlich, D. A., McCabe, M. T., Arnold, R. S., & Day, M. L. (2008) · Oncogene · doi:10.1038/onc.2008.79 · Cited by 192 · see citing works
Singh, S. V., Warin, R., Xiao, D., et al. (2009) · Cancer Research · doi:10.1158/0008-5472.can-08-3502 · Cited by 192 · see citing works
Myzak, M. C., & Dashwood, R. H. (2006) · Current Drug Targets · doi:10.2174/138945006776359467 · Cited by 161 · see citing works
γ‐Tocopherol‐enriched mixed tocopherol diet inhibits prostate carcinogenesis in TRAMP mice
Barve, A., Khor, T. O., Nair, S., et al. (2008) · International Journal of Cancer · doi:10.1002/ijc.24106 · Cited by 124 · see citing works
Keum, Y., Khor, T. O., Lin, W., Shen, G., Kwon, K. H., Barve, A., Li, W., & Kong, A. N. T. (2009) · Pharmaceutical Research · doi:10.1007/s11095-009-9948-5 · Cited by 113 · see citing works
Self-citationPinthus, J. H., Bryskin, I., Trachtenberg, J., et al. (2007) · Neoplasia · doi:10.1593/neo.06739 · Cited by 113 · see citing works
Cell death in irradiated prostate epithelial cells: role of apoptotic and clonogenic cell kill
Bromfield, G. P., Meng, A., Warde, P. R., et al. (2003) · Prostate Cancer and Prostatic Diseases · doi:10.1038/sj.pcan.4500628 · Cited by 85 · see citing works
Tanigawa, S., Lee, C., Lin, C., Ku, C., Hasegawa, H., Qin, S., Kawahara, A., Korenori, Y., Miyamori, K., Noguchi, M., et al. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.448 · Cited by 68 · see citing works
Shiota, M., Song, Y., Takeuchi, A., Yokomizo, A., Kashiwagi, E., Kuroiwa, K., Tatsugami, K., Uchiumi, T., Oda, Y., & Naito, S. (2011) · The Journal of Urology · doi:10.1016/j.juro.2011.09.147 · Cited by 61 · see citing works
Optimal treatment of intermediate‐risk prostate carcinoma with radiotherapy
Nichol, A., Warde, P. R., & Bristow, R. G. (2005) · Cancer · doi:10.1002/cncr.21257 · Cited by 56 · see citing works
A phase II study of localized prostate cancer treated to 75.6Gy with 3D conformal radiotherapy
Nichol, A., Chung, P. W. M., Lockwood, G. A., Rosewall, T., Divanbiegi, L., Sweet, J., Toi, A., Bayley, A., Bristow, R. G., Crook, J. M., et al. (2005) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2005.06.002 · Cited by 48 · see citing works
Piao, M. S., Park, J.-J., Choi, J.-Y. J., Lee, D., Yun, S. J., Lee, J.-B., & Lee, S. (2012) · Archives of Dermatological Research · doi:10.1007/s00403-012-1215-7 · Cited by 39 · see citing works
Shen, B., Wang, W., Ding, L., et al. (2014) · Human & Experimental Toxicology · doi:10.1177/0960327114530744 · Cited by 25 · see citing works
A review of clinical trials of cetuximab combined with radiotherapy for non-small cell lung cancer
Nieder, C., Pawinski, A., Dalhaug, A., et al. (2012) · Radiation Oncology · doi:10.1186/1748-717x-7-3 · Cited by 24 · see citing works
Surgery vs. radiotherapy in localized prostate cancer. Which is best?
Welz, S., Nyazi, M., Belka, C., et al. (2008) · Radiation Oncology · doi:10.1186/1748-717x-3-23 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130 · see citing works
- Authors
- Liu, M., Yao, X., Li, W., Geng, J., Yan, Y., Che, J., Xu, Y., & Zheng, J.
- Affiliations
- Tongji University (CN)
- Department of Urology, Shanghai Tenth People's Hospital Tongji University Shanghai China
- Venue
- BioFactors
- Publisher
- Wiley
- Published
- 2015-01-02
- Volume
- 41
- Issue
- 1
- Pages
- 52-57
- ISSN
- 0951-6433 (ISSN-L)
- 1872-8081
- OpenAlex
- W2160250691
- Cited by
- 27
- References
- 23
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 2
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- BioFactors (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- Nrf2, prostate cancer, radiosensitization, androgen deprivation therapy, reactive oxygen species, SFN, androgen receptor, TRAMP mice, castration, radiotherapy, oxidative stress
- MeSH terms
- Adenocarcinoma, Androgens, Animals, Castration, Gamma Rays, Humans, Male, Mice, Transgenic, Prostatic Neoplasms, Receptors, Androgen, Sulfoxides, Testosterone, Tetradecanoylphorbol Acetate, Signal Transduction, Gene Expression Regulation, Neoplastic, Anticarcinogenic Agents, Reactive Oxygen Species, Isothiocyanates, Oxidative Stress, Cell Line, Tumor, NF-E2-Related Factor 2, Mice, Androgen Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
