title: Dioscin suppresses human laryngeal cancer cells growth via induction of cell-cycle arrest and MAPK-mediated mitochondrial-derived apoptosis and inhibition of tumor invasion.
abstract: The anti-cancer effects of dioscin have been widely reported. However, its effect on laryngeal cancer remains unknown. In the present paper, our results showed that dioscin markedly caused cell apoptosis and DNA damage, increased reactive oxygen species (ROS) level, induced S-phase arrest, and inhibited invasion of human laryngeal cancer HEp-2 and TU212 cells. Mechanism investigation showed that dioscin markedly up-regulated p53 level, and down-regulated cyclin-dependent kinase 2 (CDK2) and Cyclin A levels. In addition, dioscin significantly down-regulated the levels of p-ERK, Bcl-2, up-regulated the levels of p-JNK, p-p38, Bax, cleaved caspase-3/-9, and caused Cytochrome c release. Furthermore, U0126, an ERK1/2 inhibitor, markedly down-regulated Bcl-2 level, up-regulated the levels of Bax, cleaved caspase-3/9, and enhanced Cytochrome c release inducted by dioscin. While, SP600125 (one JNK inhibitor) and SB203580 (one p38 inhibitor) markedly up-regulated Bcl-2 level, down-regulated the levels of Bax, cleaved caspase-3/9, and obviously boosted Cytochrome c release induced by dioscin. Interestingly, dioscin also markedly down-regulated the levels of MMP2 and MMP9 associated with tumor invasion. Taken together, our study indicated that dioscin suppressed laryngeal cancer cells growth via inducting cell-cycle arrest, MAPK-mediated mitochondrial- derived apoptosis and inhibiting tumor invasion, which could be used as one potential candidate for the treatment of laryngeal cancer in the future.
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors: Lingling
authors: L
authors: Si
authors: Department of Pharmaceuticals, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian 116011, China.
authors: Lingli
authors: L
authors: Zheng
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors: Lina
authors: L
authors: Xu
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors: Lianhong
authors: L
authors: Yin
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors: Xu
authors: X
authors: Han
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors: Yan
authors: Y
authors: Qi
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors: Youwei
authors: Y
authors: Xu
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors: Changyuan
authors: C
authors: Wang
authors: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Electronic address: jinyongpeng2008@126.com.
authors: Jinyong
authors: J
authors: Peng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; C019357:dioscin; D045304:Cytochromes c; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004144:Diosgenin
keywords: Apoptosis; Cell cycle arrest; Dioscin; Dioscin (PubChem CID:119245); Laryngeal cancer; Tumor invasion