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

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.

CXCR4 Blockade Enhances The Sensitivity Of Osteosarcoma To Doxorubicin By Inducing Autophagic Cell Death Via PI3K-Akt-Mtor Pathway Inhibition

“…And honokiol-induced cell death was more obviously reversed by autophagy inhibitor 3-MA compared with apoptosis inhibitor Z-VAD-FMK which indicated that honokiol-induced cell death was largely dependent on autophagic cell death (29). Besides, autophagic cell death induced by tanshinone IIA and diallyl disul de exerted inhibitory effect on 143B and MG-63 cells respectively (30,31). Consistent with these ndings, we observed that CXCR4 inhibition with or without doxorubicin induced autophagy as shown by higher expression of Beclin1 and LC3B, larger numbers of autophagosome and autolysosome, and autophagic ux activation.…”

AKR1B10 Inhibitor Epalrestat Facilitates Sorafenib-Induced Apoptosis and Autophagy Via Targeting the mTOR Pathway in Hepatocellular Carcinoma

“…Anti-apoptotic proteins Bcl2 and Bcl-xL anchor to the mitochondrial membrane through their c-terminals, preventing apoptosis through inhibiting mitochondrial membrane permeability and cytochrome c release [26]. Because apoptosis plays an important role in tutor occurrence, development, and prognosis, anti-tumour therapy often targets apoptosis promotion [27]. Our results revealed that compared with monotherapy, combination treatment significantly increased total HepG2 apoptotic rate, along with Bax and cleaved caspase 3 expression, while decreasing Bcl-2 expres-sion.…”

Silencing of SPP1 Suppresses Progression of Tongue Cancer by Mediating the PI3K/Akt Signaling Pathway

“…Cell signaling plays an important role in tumor development. The PI3K/Akt pathway is considered to be the primary pathway for cancer cell survival, which is called the “anti-apoptosis pathway.” 31 PI3 K is an intracellular phosphopeptide kinase discovered by Ito et al (2010), which is related to the products of the v-Src and v-Ars oncogenes. 32 PI3 K itself has serine/threonine kinase activity.…”