title: A monomer purified from Paris polyphylla (PP-22) triggers S and G2/M phase arrest and apoptosis in human tongue squamous cell carcinoma SCC-15 by activating the p38/cdc25/cdc2 and caspase 8/caspase 3 pathways.
abstract: Recent studies have shown that the aqueous, ethanolic extracts and a monomer compound of Paris polyphylla exhibit anticancer activity toward several types of cancer cell lines, but the anticancer activity of (3β,17α,25R)-spirost-5-ene-3,17-diol 3-O-α-L-rhamnopyranosyl-(1 → 2)-β-D-glucopyranoside, a monomer isolated from P. polyphylla (PP), named PP-22, has not been reported previously. In this study, we investigated the effect of PP-22 on human tongue squamous cell carcinoma SCC-15 cells in vitro. MTT assays showed that PP-22 inhibited the growth of SCC-15 cells and had no obvious inhibitory effects on human liver L02 cells. Flow cytometry assays showed that the percentages of apoptotic cells were increased. In addition, cleaved caspase-8, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) could be detected by Western blotting. Flow cytometry also showed that PP-22 triggered S and G2/M phases arrest in SCC-15 cells, and on the other hand, the expression of cyclin A, cyclin E2, cyclin B1, phospho-cell division cycle2 (p-cdc2)(Tyr15), p-Wee1, Myt1, and p53 was upregulated. Moreover, p-p38 levels increased, p-extracellular signal-regulated kinase (ERK) levels decreased, and cdc25B expression was inhibited. Furthermore, the p38/mitogen-activated protein kinase (MAPK) inhibitor SB203580 reversed the increase of the expression level of p38, p-cdc2 (Tyr15), cleaved caspase 3, cleaved PARP, p-p53, and p53 and reversed the decrease in cdc25B expression. In conclusion, these results demonstrated that PP-22 activated p38, inhibited cdc25B, increased p-cdc2 (Tyr15), and triggered S and G2/M phase arrest, as well as activated p53 through the p38-p53 pathway, inhibited the MAPK/ERK pathway, activated the caspase 8/caspase 3 pathway, and triggered the extrinsic apoptotic pathway in SCC-15 cells.
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.|Department of Orthodontics, Foshan Chancheng Stomatological Hospital, Foshan, 528000, China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Ke
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Clinical Medicine, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Rui-Song
authors.initials: RS
authors.lastname: Gong
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Wan-Jing
authors.initials: WJ
authors.lastname: Cen
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
authors.forename: Hui-Qun
authors.initials: HQ
authors.lastname: Huang
authors.affiliation: Department of Orthodontics, Foshan Chancheng Stomatological Hospital, Foshan, 528000, China.
authors.forename: Ye-Rong
authors.initials: YR
authors.lastname: Li
authors.affiliation: Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. tkongwd@jnu.edu.cn.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Kong
authors.affiliation: Department of Clinical Medicine, Medical College, Jinan University, Guangzhou, 510632, China. jjw703@163.com.|Department of Biochemistry, Medical College, Jinan University, Guangzhou, 510630, China. jjw703@163.com.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Jiang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056750:Cyclin A1 / Q000096:biosynthesis; D056744:Cyclin B1 / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D000070556:Melanthiaceae / Q000378:metabolism; D009687:Nuclear Proteins; D010936:Plant Extracts / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases; D011725:Pyridines / Q000494:pharmacology; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D012503:Saponins / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000188:drug therapy; D014157:Transcription Factors / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D020687:cdc25 Phosphatases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C503745:CCNA1 protein, human; C534699:CCNB1 protein, human; C503688:CCNE2 protein, human; D018797:Cell Cycle Proteins; D056750:Cyclin A1; D056744:Cyclin B1; D016213:Cyclins; D004268:DNA-Binding Proteins; D007093:Imidazoles; C078341:MYT1 protein, human; D009687:Nuclear Proteins; D010936:Plant Extracts; D011725:Pyridines; D012503:Saponins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C000614447:spirost-5-ene-3,17-diol 3-O-rhamnopyranosyl-(1-2)-glucopyranoside; D011065:Poly(ADP-ribose) Polymerases; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C517004:CDC25A protein, human; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases; D053148:Caspase 3; D053181:Caspase 8; C093642:SB 203580
keywords: Apoptosis; Cell cycle arrest; Rhizoma paridis; SCC-15 cells; p38