title: Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen species-mediated downregulation of the PI3K/Akt pathway.
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.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Shandong Institute of Medicine and Health Information, Shandong Academy of Medical Sciences, Ji'nan, Shandong 250062, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Ka
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Emergency, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Jiguang
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D019938:Cyclin D1 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D000111:Acetylcysteine; D000498:Allyl Compounds; D000970:Antineoplastic Agents; D000975:Antioxidants; D002867:Chromones; D019938:Cyclin D1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D013440:Sulfides; C530104:CCND1 protein, human; C042577:diallyl trisulfide; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one