Abstract

Diallyl disulfide (DADs), a natural organic compound, is extracted from garlic and scallion and has anti-tumor effects against various tumors. This study investigated the anti-tumor activity of DADs in human osteosarcoma cells and the mechanisms. MG-63 cells were exposed to DADs (0, 20, 40, 60, 80, and 100 μM) for different lengths of time (24, 48, and 72 h). The CCK8 assay results showed that DADs inhibited osteosarcoma cell viability in a dose-and time-dependent manner. FITC-Annexin V/propidium iodide staining and flow cytometry demonstrated that the apoptotic ratio increased and the cell cycle was arrested at the G2/M phase as the DADs concentration was increased. A Western blot analysis was employed to detect the levels of caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and p62 as well as suppression of the mTOR pathway. High expression of LC3-II protein revealed that DADs induced formation of autophagosome. Furthermore, DADs-induced apoptosis was weakened after adding 3-methyladenine, demonstrating that the DADs treatment resulted in autophagy-mediated death of MG-63 cells. In addition, DADs depressed p-mTOR kinase activity, and the inhibited PI3K/Akt/mTOR pathway increased DADs-induced apoptosis and autophagy. In conclusion, our results reveal that DADs induced G2/M arrest, apoptosis, and autophagic death of human osteosarcoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

Highlights

  • Osteosarcoma (OS) is one of the most frequent bone malignancies, developing from the bone-forming mesenchymal cell lines

  • MG-63 cells were treated with different concentrations of Diallyl disulfide (DADs) (0, 20, 40, 60, 80, and 100 μM) for 12, 48, and 72 h

  • Cell viability was measured with the Cell Counting Kit-8 (CCK-8) assay

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Summary

Introduction

Osteosarcoma (OS) is one of the most frequent bone malignancies, developing from the bone-forming mesenchymal cell lines. The reality is that the drug resistance of tumors is becoming more and more complex, so new anti-cancer drugs are urgently needed

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Conclusion

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