|
[PMID]: | 27644244 |
[Au] Autor: | Ke JY; Zhang W; Gong RS; Cen WJ; Huang HQ; Li YR; Kong WD; Jiang JW |
[Ad] Endereço: | Department of Stomatology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China. |
[Ti] Título: | 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. |
[So] Source: | Tumour Biol;37(11):14863-14872, 2016 Nov. | [Is] ISSN: | 1423-0380 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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 (3ß,17α,25R)-spirost-5-ene-3,17-diol 3-O-α-L-rhamnopyranosyl-(1 → 2)-ß-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. |
[Mh] Termos MeSH primário: |
Caspase 3/metabolismo Caspase 8/metabolismo Quinases Ciclina-Dependentes/metabolismo Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos Saponinas/farmacologia Fosfatases cdc25/metabolismo Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
|
[Mh] Termos MeSH secundário: |
Antineoplásicos Fitogênicos/farmacologia Apoptose/efeitos dos fármacos Proteína Quinase CDC2 Carcinoma de Células Escamosas/tratamento farmacológico Proteínas de Ciclo Celular Linhagem Celular Tumoral Proliferação Celular/efeitos dos fármacos Ciclina A1/biossíntese Ciclina B1/biossíntese Ciclinas/biossíntese Proteínas de Ligação a DNA/biossíntese Seres Humanos Imidazóis/farmacologia Melanthiaceae/metabolismo Proteínas Nucleares Extratos Vegetais/farmacologia Poli(ADP-Ribose) Polimerases/metabolismo Proteínas Tirosina Quinases Piridinas/farmacologia Neoplasias da Língua/tratamento farmacológico Fatores de Transcrição/biossíntese Proteína Supressora de Tumor p53/biossíntese Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores
|
[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Antineoplastic Agents, Phytogenic); 0 (CCNA1 protein, human); 0 (CCNB1 protein, human); 0 (CCNE2 protein, human); 0 (Cell Cycle Proteins); 0 (Cyclin A1); 0 (Cyclin B1); 0 (Cyclins); 0 (DNA-Binding Proteins); 0 (Imidazoles); 0 (MYT1 protein, human); 0 (Nuclear Proteins); 0 (Plant Extracts); 0 (Pyridines); 0 (Saponins); 0 (Transcription Factors); 0 (Tumor Suppressor Protein p53); 0 (spirost-5-ene-3,17-diol 3-O-rhamnopyranosyl-(1-2)-glucopyranoside); EC 2.4.2.30 (Poly(ADP-ribose) Polymerases); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.2 (WEE1 protein, human); EC 2.7.11.22 (CDC2 Protein Kinase); EC 2.7.11.22 (CDK1 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinases); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.1.3.48 (CDC25A protein, human); EC 3.1.3.48 (CDC25B protein, human); EC 3.1.3.48 (cdc25 Phosphatases); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 8); OU13V1EYWQ (SB 203580) |
[Em] Mês de entrada: | 1702 |
[Cu] Atualização por classe: | 171116 |
[Lr] Data última revisão:
| 171116 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 160921 |
[St] Status: | MEDLINE |
|
|
|