Psoralen induced cell cycle arrest by modulating Wnt/β-catenin pathway in breast cancer cells

Scientific Reports

Xiaohong Wang¹  Yitong Hua¹  Yingzhe Zhang¹  Shujian Xu¹  Kai Cheng¹  Guoqiang Zhang¹  Chengfeng Xu¹  Song Liu¹  Jian Liu¹  Zhenlin Yang¹  Yong Han¹ 

[1] Department of Thyroid and Breast Surgery, Binzhou Medical University Hospital;

关键词: Breast Cancer;    Cell Cycle;    Psoralen Treatment;    Plate Colony Formation Assay;    Relative Target Gene;   

DOI  :  10.1038/s41598-018-32438-7

来源: DOAJ

【 摘 要 】

Abstract Psoralen could inhibit the proliferation of human breast cancer cells, however, the molecular mechanism was unclear. We evaluated the anti-proliferative effects of psoralen by MTT, plate colony formation assay and cell cycle analysis in MCF-7 and MDA-MB-231 cells. The effects of psoralen on activation of Wnt/β-catenin and the related target genes were examined by quantitative real-time PCR, western blotting and cell immunofluorescence. The tumor growth was conducted in BALB/c nude mice and the pathological changes of heart, liver and kidney were also observed. Our results demonstrate that psoralen significantly inhibited cell proliferation by inducing G0/G1 phase arrest in MCF-7 cells and G2/M phase arrest in MDA-MB-231 cells. The expression of Fra-1 was reduced and Axin2 was promoted both in MCF-7 and MDA-MB-231 cells after psoralen treatment. The cytoplasmic accumulation and nuclear translocation of β-catenin were significantly reduced by psoralen. Psoralen increased the levels of phospho-(Y142) β-catenin, while decreased the expression of total β-catenin and its downstream target Fra-1 in vitro and vivo. Moreover, psoralen didn’t cause any significant toxicity at the effective concentration. Overall, our results might provide theoretical basis for clinical application of psoralen in breast cancer.

【 授权许可】

Unknown