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Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen species-mediated downregulation of the PI3K/Akt pathway.
Oncol Rep 2016; 35(6):3648-58OR

Abstract

Diallyl trisulfide (DATS) is a natural organosulfur compound isolated from garlic, and has been reported to possess anticancer activities. However, the cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma cells have not been well studied. The present study demonstrated that DATS significantly reduced cell viability in a dose- and time-dependent manner in MG63 and MNNG/HOS cells. DATS-induced G0/G1 phase arrest was found to correlate with a decrease in cyclin D1 in concomitance with an increase in p21 and p27. DATS induced a marked increase in reactive oxygen species (ROS) levels and collapse of mitochondrial membrane potential (Δψm) in the osteosarcoma cells. DATS induced apoptosis in the MG63 and MNNG/HOS cells via inhibition of the PI3K/Akt signaling pathway and through the mitochondrial apoptotic pathway. The efficiency of DATS basically approached the efficacy of LY294002, a specific PI3K inhibitor. However, N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the DATS-induced ROS increase, inhibition of the PI3K/Akt pathway and cell apoptosis. Overall, DATS has the potential to be developed as a new anticancer drug. The mechanisms of action involve the ROS-mediated downregulation of the PI3K/Akt pathway.

Authors+Show Affiliations

Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.Shandong Institute of Medicine and Health Information, Shandong Academy of Medical Sciences, Ji'nan, Shandong 250062, P.R. China.Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.Department of Emergency, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27035545

Citation

Wang, Hongliang, et al. "Diallyl Trisulfide Induces Osteosarcoma Cell Apoptosis Through Reactive Oxygen Species-mediated Downregulation of the PI3K/Akt Pathway." Oncology Reports, vol. 35, no. 6, 2016, pp. 3648-58.
Wang H, Sun N, Li X, et al. Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen species-mediated downregulation of the PI3K/Akt pathway. Oncol Rep. 2016;35(6):3648-58.
Wang, H., Sun, N., Li, X., Li, K., Tian, J., & Li, J. (2016). Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen species-mediated downregulation of the PI3K/Akt pathway. Oncology Reports, 35(6), pp. 3648-58. doi:10.3892/or.2016.4722.
Wang H, et al. Diallyl Trisulfide Induces Osteosarcoma Cell Apoptosis Through Reactive Oxygen Species-mediated Downregulation of the PI3K/Akt Pathway. Oncol Rep. 2016;35(6):3648-58. PubMed PMID: 27035545.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen species-mediated downregulation of the PI3K/Akt pathway. AU - Wang,Hongliang, AU - Sun,Na, AU - Li,Xin, AU - Li,Ka, AU - Tian,Jiguang, AU - Li,Jianmin, Y1 - 2016/04/01/ PY - 2016/02/04/received PY - 2016/03/15/accepted PY - 2016/4/2/entrez PY - 2016/4/2/pubmed PY - 2017/3/14/medline SP - 3648 EP - 58 JF - Oncology reports JO - Oncol. Rep. VL - 35 IS - 6 N2 - Diallyl trisulfide (DATS) is a natural organosulfur compound isolated from garlic, and has been reported to possess anticancer activities. However, the cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma cells have not been well studied. The present study demonstrated that DATS significantly reduced cell viability in a dose- and time-dependent manner in MG63 and MNNG/HOS cells. DATS-induced G0/G1 phase arrest was found to correlate with a decrease in cyclin D1 in concomitance with an increase in p21 and p27. DATS induced a marked increase in reactive oxygen species (ROS) levels and collapse of mitochondrial membrane potential (Δψm) in the osteosarcoma cells. DATS induced apoptosis in the MG63 and MNNG/HOS cells via inhibition of the PI3K/Akt signaling pathway and through the mitochondrial apoptotic pathway. The efficiency of DATS basically approached the efficacy of LY294002, a specific PI3K inhibitor. However, N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the DATS-induced ROS increase, inhibition of the PI3K/Akt pathway and cell apoptosis. Overall, DATS has the potential to be developed as a new anticancer drug. The mechanisms of action involve the ROS-mediated downregulation of the PI3K/Akt pathway. SN - 1791-2431 UR - https://www.unboundmedicine.com/medline/citation/27035545/Diallyl_trisulfide_induces_osteosarcoma_cell_apoptosis_through_reactive_oxygen_species_mediated_downregulation_of_the_PI3K/Akt_pathway_ L2 - http://www.spandidos-publications.com/or/35/6/3648 DB - PRIME DP - Unbound Medicine ER -