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Alpinumisoflavone Causes DNA Damage In Colorectal Cancer Cells Via Blocking DNA Repair Mediated By RAD51
Published 2019 · Biology, Medicine
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Aims: Colorectal Cancer (CRC) accounts for 6.1% incidence and 9.2% mortality worldwide. The current study aimed to investigate the effect of alpinumisoflavone (AIF) on CRC and its possible molecular mechanism. Methods: HCT‐116 and SW480 cells were chosen as cell model to study the anti‐cancer activity of AIF in vitro experiments. Cells proliferative capacity and clonogenicity were examined by CCK‐8 assay and colony formation assay, while cell apoptosis was detected by Hoechst 33258 staining and Flow cytometer. The protein expression levels of related gene were examined by western blotting. Transcriptome analyses were conducted to identify the differentially expressed genes in CRC cells, following AIF treatment. DNA damage was examined by &ggr;H2AX foci assay. The anti‐cancer effect of AIF in vivo was validated in CRC xenograft model. Key findings: We found that AIF inhibited CRC cell proliferation and promoted apoptosis in a dose‐dependent manner, as well as increased the number of &ggr;‐H2AX foci. In addition, microarray analysis showed that the DNA‐double strand break (DSB) repair gene RAD51 was aberrantly overexpressed in CRC tissues, and was positively correlated with lymph node metastasis, TNM stage and poor outcomes. Both in vitro and in vivo experiments confirm that AIF treatment significantly decreased RAD51 levels. Knockdown RAD51 could enhance the anti‐cancer activity of AIF against CRC, while abrogated by RAD51 overexpression. Significance: These findings suggest that AIF can be regarded as a potential anti‐cancer drug and provide new insights into CRC treatment.