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Published on: October 28, 2021
Diallyl trisulfide inhibits osteosarcoma 143B cell migration, invasion and EMT by inducing autophagy
Xiyu Liu1, Nan Wang1, Zhiwei He1
1The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China.
Background:
Diallyl trisulfide (DATS), a compound derived from garlic, has been demonstrated its anti-cancer properties. While it has been shown to inhibit the expression of epidermal growth factor receptor (EGFR) in various cancers, its effects on osteosarcoma (OS) cells remain unclear. This study aimed to investigate the impacts of DATS on OS cells growth, migration, invasion, epithelial-mesenchymal transition (EMT) and autophagy, as well as its underlying mechanisms which was involving in the EGFR/PI3K/AKT/mTOR pathway.
Methods:
In this study, human osteosarcoma cells (143B) were treated with different concentrations of DATS (10, 50, 100 and 200 μM) for 24 and 48 h, respectively. Cell viability was measured using CCK8, the half lethal concentration was selected for the following experiments. Wound healing and transwell assays were performed to evaluate migration and invasion abilities, while flow cytometry was used to measure apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and confocal imaging were employed to analyze the related mRNA and protein expression levels of epithelial-mesenchymal transition (EMT), EGFR/Phosphoinositide 3 kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related markers.
Results:
DATS significantly inhibited proliferation, migration and EMT in osteosarcoma cells. Additionally, DATS promoted cell apoptosis and induced autophagy, which could be rescued by the autophagy inhibitor 3-methyladenine (3-MA). Moreover, DATS treatment led to the inactivation of the EGFR/PI3K/AKT/mTOR pathway in osteosarcoma cells.
Conclusions:
This study demonstrated that DATS inhibited osteosarcoma cell growth, migration and EMT, but inducing apoptosis and autophagy. These effects were mediated by the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway. These findings suggested that DATS could serve as a potential therapeutic agent for osteosarcoma treatment.
Insights
Diallyl trisulfide (DATS) inhibits osteosarcoma cell growth, migration, and EMT while promoting apoptosis and autophagy. These effects are linked to the inactivation of the EGFR/PI3K/AKT/mTOR pathway, suggesting DATS as a potential osteosarcoma therapeutic.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Diallyl trisulfide (DATS), a garlic-derived compound, exhibits anti-cancer properties.
- Its effect on osteosarcoma (OS) cells, particularly regarding EGFR signaling, is not well understood.
- Investigating DATS's impact on OS cell proliferation, migration, invasion, EMT, and autophagy is crucial.
Purpose of the Study:
- To investigate the effects of Diallyl trisulfide (DATS) on osteosarcoma (OS) cell behavior.
- To elucidate the underlying mechanisms involving the EGFR/PI3K/AKT/mTOR pathway and autophagy.
- To assess the potential of DATS as a therapeutic agent for osteosarcoma.
Main Methods:
- Human osteosarcoma cells (143B) were treated with varying DATS concentrations.
- Cell viability, migration, invasion, and apoptosis were assessed using CCK8, wound healing, Transwell assays, and flow cytometry.
- Gene and protein expression related to EMT, the EGFR/PI3K/AKT/mTOR pathway, and autophagy were analyzed via qRT-PCR, Western blotting, and confocal imaging.
Main Results:
- DATS significantly inhibited osteosarcoma cell proliferation, migration, and epithelial-mesenchymal transition (EMT).
- DATS induced apoptosis and autophagy in osteosarcoma cells, with autophagy being reversible by 3-MA.
- Treatment with DATS led to the inactivation of the EGFR/PI3K/AKT/mTOR signaling pathway.
Conclusions:
- DATS effectively inhibits osteosarcoma cell growth, migration, and EMT.
- The anti-cancer effects of DATS are mediated through the inactivation of the EGFR/PI3K/AKT/mTOR pathway and induction of autophagy.
- DATS demonstrates potential as a therapeutic agent for osteosarcoma treatment.
