Journal Article

Diallyl Disulfide Induces Apoptosis and Autophagy in Human Osteosarcoma MG-63 Cells through the PI3K/Akt/mTOR Pathway

Xin Guan, Dongfang Li, Ziqi Yue, Shanshan Liu, Rui Chao, Panpan Yang, Minqi Li, Tomoka Hasegawa, Cancan Huang, Jie Guo

2019

Overview

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.

• Publisher: MDPI AG,MDPI
• Subject: Allyl Compounds / Allyl Compounds - isolation & purification / Allyl Compounds - pharmacology / Antineoplastic Agents, Phytogenic / Antineoplastic Agents, Phytogenic - isolation & purification / Antineoplastic Agents, Phytogenic - pharmacology / Apoptosis / Apoptosis - drug effects / Apoptosis - genetics / Autophagosomes / Autophagosomes - drug effects / Autophagosomes - metabolism / Autophagy / Autophagy - drug effects / Autophagy - genetics / bcl-2-Associated X Protein / bcl-2-Associated X Protein - genetics / bcl-2-Associated X Protein - metabolism / Bone cancer / Cancer therapies / Caspase 3 / Caspase 3 - genetics / Caspase 3 - metabolism / Cell cycle / Cell division / Cell growth / Cell Line, Tumor / Chemotherapy / diallyl disulfide / Disulfides / Disulfides - isolation & purification / Disulfides - pharmacology / Drug dosages / Flow cytometry / G2 Phase Cell Cycle Checkpoints / G2 Phase Cell Cycle Checkpoints - drug effects / G2 Phase Cell Cycle Checkpoints - genetics / Garlic / Garlic - chemistry / Gene Expression Regulation, Neoplastic / Homeostasis / Humans / Kinases / Microtubule-Associated Proteins / Microtubule-Associated Proteins - genetics / Microtubule-Associated Proteins - metabolism / Organic chemistry / Osteoblasts / Osteoblasts - drug effects / Osteoblasts - metabolism / Osteoblasts - pathology / osteosarcoma / Phosphatidylinositol 3-Kinases / Phosphatidylinositol 3-Kinases - genetics / Phosphatidylinositol 3-Kinases - metabolism / PI3K/Akt/mTOR pathway / Protein expression / Proteins / Proto-Oncogene Proteins c-akt / Proto-Oncogene Proteins c-akt - genetics / Proto-Oncogene Proteins c-akt - metabolism / Proto-Oncogene Proteins c-bcl-2 / Proto-Oncogene Proteins c-bcl-2 - genetics / Proto-Oncogene Proteins c-bcl-2 - metabolism / QD241-441 / Sarcoma / Sequestosome-1 Protein / Sequestosome-1 Protein - genetics / Sequestosome-1 Protein - metabolism / Signal Transduction / TOR Serine-Threonine Kinases / TOR Serine-Threonine Kinases - genetics / TOR Serine-Threonine Kinases - metabolism / Tumors