ReferenceID 5462
Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models
Int J Mol Sci
Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use
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- Reference Id
- 5462
- Evidence Id
- 22052
- Core Evidence Id
- 22052
- Source Reference Id
- 4175
- Herb2 Reference Id
- HBREF004972
- Subject Paper Key
- HBIN029720_34575923
- Pubmed Id
- 34575923
- Doi
- 10.3390/ijms22189766
- Paper Title
- Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models
- Paper Abstract
- Molecules involved in DNA damage response (DDR) are often overexpressed in cancer cells, resulting in poor responses to chemotherapy and radiotherapy. Although treatment efficacy can be improved with the concomitant use of DNA repair inhibitors, the accompanying side effects can compromise the quality of life of patients. Therefore, in this study, we identified a natural compound that could inhibit DDR, using the single-strand annealing yeast-cell analysis system, and explored its mechanisms of action and potential as a chemotherapy adjuvant in hepatocellular carcinoma (HCC) cell lines using comet assay, flow cytometry, Western blotting, immunofluorescence staining, and functional analyses. We developed a mouse model to verify the in vitro findings. We found that hydroxygenkwanin (HGK) inhibited the expression of RAD51 and progression of homologous recombination, thereby suppressing the ability of the HCC cell lines to repair DNA damage and enhancing their sensitivity to doxorubicin. HGK inhibited the phosphorylation of DNA damage checkpoint proteins, leading to apoptosis in the HCC cell lines. In the mouse xenograft model, HGK enhanced the sensitivity of liver cancer cells to doxorubicin without any physiological toxicity. Thus, HGK can inhibit DDR in liver cancer cells and mouse models, making it suitable for use as a chemotherapy adjuvant.
- Journal
- Int J Mol Sci
- Publish Year
- 2021
- Experiment Subject
- mouse; patient; hcc cell lines; hepatocellular carcinoma (hcc) cell lines; yeast
- Experiment Type
- Animal Experiment
- Phenotype Related
- Liver Cancer; Cancer; Hepatocellular Carcinoma
- Paper Title Cn
- Paper Title En
- Hydroxygenkwanin Increases the Sensitivity of Liver Cancer Cells to Chemotherapy by Inhibiting DNA Damage Response in Mouse Xenograft Models
- Bilingual Status
- semi_complete