The antitumour activity of chrysin have been studied in several types of cancer cells. In urinary bladder cancer, its cytotoxic effects have already demonstrated; however, its mechanism of action is not completely understood and the role of tumour protein p53 (TP53) gene in these effects is unclear. In this study, we investigated the role of chrysin (10, 20, 40, 60 80 and 100 µM) in progression of bladder tumour cells with different status of the TP53 gene and different degrees of tumour (RT4, grade 1, TP53 wild type; 5637, grade 2, TP53 mutated and T24, grade 3, TP53 mutated). Results demonstrated that chrysin inhibited cell proliferation by increasing reactive oxygen species and DNA damage and inhibited cell migration in all cell lines. In TP53 wild-type cells, a sub-G1 apoptotic population was present. In mutated TP53 cells, chrysin caused arrest at the G2/M phase and morphological changes accompanied by downregulation of PLK1, SRC and HOXB3 genes. In addition, in Grade 2 cells, chrysin induced global DNA hypermethylation and, in the highest-grade cells, downregulated c-MYC, FGFR3 and mTOR gene expression. In conclusion, chrysin has antiproliferative and toxicogenetic activity in bladder tumour cells independently of TP53 status; however, the mechanisms of action are dependent on TP53 status.

中文翻译：

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菊花蛋白在膀胱癌细胞中的毒性和抗增殖作用。

在几种类型的癌细胞中已经研究了菊花素的抗肿瘤活性。在膀胱癌中，已经证明了其细胞毒性作用。然而，其作用机理尚不完全清楚，肿瘤蛋白p53（TP53）基因在这些作用中的作用尚不清楚。在这项研究中，我们研究了Chrysin（10、20、40、60 80和100 µM）在具有不同TP53基因状态和不同程度肿瘤（RT4、1级，TP53野生型）的膀胱肿瘤细胞进程中的作用; 5637，等级2，TP53突变，T24，等级3，TP53变异）。结果表明，Chrysin通过增加活性氧和DNA损伤来抑制细胞增殖，并抑制所有细胞系中的细胞迁移。在TP53野生型细胞中，存在亚G1细胞凋亡。在突变的TP53细胞中，chrysin导致G2 / M期停滞，形态变化伴随PLK1，SRC和HOXB3基因的下调。此外，在2级细胞中，chrysin诱导了整体DNA的高度甲基化，而在最高等级的细胞中，其下调了c-MYC，FGFR3和mTOR基因的表达。结论：chrysin在膀胱肿瘤细胞中具有独立于TP53的抗增殖和致毒活性状态; 但是，其作用机制取决于TP53的状态。