Genistein‐induced DNA damage is repaired by nonhomologous end joining and homologous recombination in TK6 cells
Abstract
Genistein (GES), a phytoestrogen, has potential chemopreventive and chemotherapeutic effects on cancer. The anticancer mechanism of GES may be related with topoisomerase II associated DNA double‐strand breaks (DSBs). However, the precise molecular mechanism remains elusive. Here, we performed genetic analyses using human lymphoblastoid TK6 cell lines to investigate whether non‐homologous DNA end joining (NHEJ) and homologous recombination (HR), the two major repair pathways of DSBs, were involved in repairing GES‐induced DNA damage. Our results showed that GES induced DSBs in TK6 cells. Cells lacking Ligase4, an NHEJ enzyme, are hypersensitive to GES. Furthermore, the sensitivity of Ligase4−/− cells was associated with enhanced DNA damage when comparing the accumulation of γ‐H2AX foci and number of chromosomal aberrations (CAs) with WT cells. In addition, cells lacking Rad54, a HR enzyme, also presented hypersensitivity and increased DNA damages in response to GES. Meanwhile, Treatment of GES‐lacking enhanced the accumulation of Rad51, an HR factor, in TK6 cells, especially in Ligase4−/−. These results provided direct evidence that GES induced DSBs in TK6 cells and clarified that both NHEJ and HR were involved in the repair of GES‐induced DNA damage, suggesting that GES in combination with inhibition of NHEJ or HR would provide a potential anticancer strategy.
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Genistein has the potential to amplify the activity of drugs targeting DNA damage, including inhibitors of the NHEJ and HR pathways.
“suggested that genistein has the potential to amplify the activity of drugs targeting DNA damage including inhibitors of the NHEJ and HR pathways.”
From Drug repurposing for cancer therapy (2024) · cites this paper as [173]
Genistein may be a potential adjuvant in therapeutic strategies that exploit the DNA damage response for cancer treatment.
“Thus, genistein may be a potential adjuvant in therapeutic strategies that exploit the DDR for cancer treatment.173”
From Drug repurposing for cancer therapy (2024) · cites this paper as [173]
NHEJ and homologous recombination collaborate in the repair of genistein-induced DNA damage.
“These findings not only highlighted the collaborative roles of NHEJ and homologous recombination (HR) in the repair of genistein-induced DNA damage”
From Drug repurposing for cancer therapy (2024) · cites this paper as [173]
Genistein induces DNA damage in human lymphoblastoid TK6 cells.
“One pivotal study demonstrated that genistein induced DNA damage in human lymphoblastoid TK6 cells.”
From Drug repurposing for cancer therapy (2024) · cites this paper as [173]
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- Authors
- Hu, X., Wu, X., Liu, H., Cheng, Z., Zhao, Z., Xiang, C., Feng, X., Takeda, S., & Qing, Y.
- Affiliations
- Sichuan University (CN)
- Kyoto University (JP)
- Corresponding author
- Wu, Xiaohua
- Qing, Yong
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2018-08-02
- Volume
- 234
- Issue
- 3
- Pages
- 2683-2692
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W2887418817
- Cited by
- 9
- References
- 51
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 1
- FWCI
- 0.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81373431)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- genistein, DNA double-strand breaks, DNA repair, non-homologous end joining, homologous recombination, Rad54, RAD51, topoisomerase II, phytoestrogens, TK6 cells, γH2AX foci, chromosomal abnormalities, chemoprevention
- MeSH terms
- Cell Cycle, Cell Line, DNA Damage, DNA Repair, DNA-Binding Proteins, Humans, Genistein, DNA Breaks, Double-Stranded, Homologous Recombination, DNA End-Joining Repair
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