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Diallyl trisulfide regulates cell apoptosis and invasion in human osteosarcoma U2OS cells through regulating
Pan He1, Zhijun Wang2, Bin Sheng2
1The Department of Traumatic and Osteopathology, Hunan provincial people's hospital, Changsha, Hunan, China. h13487490749@126.com.
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 E-cadherin. 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.
Insights
Diallyl trisulfide (DATS) effectively inhibits osteosarcoma (OS) cell proliferation and metastasis by inducing apoptosis and regulating key signaling pathways. This natural compound shows promise as a potential therapeutic agent for OS treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma (OS) is a primary bone malignancy with a high propensity for metastasis.
- Effective therapeutic strategies for OS, particularly targeting proliferation and metastasis, are urgently needed.
- Natural compounds are being explored for their potential anticancer properties.
Purpose of the Study:
- To investigate the effects of Diallyl trisulfide (DATS) on the proliferation and metastasis of human osteosarcoma (OS) U2OS cells.
- To elucidate the underlying mechanisms of action of DATS in OS.
Main Methods:
- U2OS cells were treated with varying concentrations of DATS.
- Cell proliferation was assessed using MTT assays.
- Apoptosis and cell cycle distribution were analyzed by flow cytometry (FCM).
- Migration and invasion were evaluated using wound healing and Transwell assays.
- In vivo efficacy was tested in a mouse OS xenograft model.
Main Results:
- DATS exhibited a time- and concentration-dependent cytotoxic effect on U2OS cells.
- DATS induced apoptosis and G0/G1 cell cycle arrest.
- DATS significantly inhibited cell migration and invasion in vitro.
- In vivo studies showed reduced tumor volume, weight, and lung metastasis in DATS-treated mice.
- DATS modulated the expression of key proteins involved in cell survival and metastasis, including the PI3K/AKT/GSK3β pathway.
Conclusions:
- DATS effectively inhibits osteosarcoma progression by suppressing cell proliferation, migration, and invasion.
- The anticancer effects of DATS are mediated through the regulation of PI3K/AKT/GSK3β signaling pathways.
- DATS demonstrates potential as a therapeutic agent for osteosarcoma, either as a standalone treatment or in combination therapy.
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