Publication: Diallyl trisulfide regulates cell apoptosis and
invasion in human osteosarcoma U2OS cells through
regulating PI3K/AKT/GSK3β signaling pathway
Authors
He, Pan ; Wang, Zhijun ; Sheng, Bin ; Xu, Yongqiang ; Feng, Siyin ; Huang, Yan ; Gong, Fuqiang ; Tang, Liting ; Xie, Liming
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-299
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info:eu-repo/semantics/article
Description
Abstract
Aims. To investigate the effects and the
mechanisms of action of Diallyl trisulfide (DATS) on the
proliferation and metastasis of human osteosarcoma
(OS) U2OS.
Methods. U2OS cells were treated by different
concentrations of DATS at different time points. Cell
proliferations were measured by MTT assay. DATS
induced cell cycle distribution and apoptosis were
evaluated by flow cytometry (FCM) with Annexin-V.
Cell migration and invasion were detected by wound
healing assay and transwell assay. The effects of DATS
in U2OS cell growth and metastasis were also detected
in a mouse OS xenograft model.
Results. A time- and concentration-dependent
cytotoxic effect of DATS was observed in U2OS cells.
FCM with PI staining and Annexin-V -FITC indicated
that DATS induces apoptosis and a G0/G1 cell cycle
arrest of U2OS cells at all concentrations from 25 μmol/l
to 100 μmol/l. DATS also inhibits the migration and
invasion of U2OS cells. Western blot showed that the
expression levels of p-AKT, p-GSK3β, Bcl-2, Vimentin
and β-catenin were decreased, while the expression levels
of Bad, Bax and E-cadherin were significantly increased
in DATS treated U2OS cells. Analysis using a mouse
xenograft model indicated that xenografts of DATS
treatment group had a significant decrease in tumor
volume and weight compared to the control group. Lung
metastasis models in mice demonstrated that treatment of
DATS inhibits lung metastasis of OS in vivo.
Conclusions. These data suggested that DATS
inhibits OS development and progression through the
regulation of PI3K/AKT/GSK3β signaling pathways,
accompanied by downregulation of Bcl-2, Vimentin and
β-catenin, as well as upregulation of Bad, Bax and Ecadherin. Therefore, our data demonstrated that DATS
exerted its anticancer effects by inhibiting cell
proliferation, migration and invasion in vitro and in vivo.
These results provide evidence for the use of the natural
product DATS either alone or in combination with
standard therapy for OS.
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Citation
Histology and Histopathology Vol. 35, nº12 (2020)
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