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

Autor: Jun-Yu Ke, Hui-Qun Huang, Rui-Song Gong, Wu Zhang, Wei-Dong Kong, Wan-Jing Cen, Ye-Rong Li, Jian-Wei Jiang
Rok vydání: 2016
Předmět:
0301 basic medicine
MAPK/ERK pathway
Pyridines
Poly ADP ribose polymerase
Cyclin A
Apoptosis
Cell Cycle Proteins
Caspase 3
Biology
Caspase 8
p38 Mitogen-Activated Protein Kinases
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Cyclins
CDC2 Protein Kinase
Humans
cdc25 Phosphatases
Cyclin B1
Cell Proliferation
Cyclin-dependent kinase 1
Plant Extracts
Imidazoles
Nuclear Proteins
General Medicine
Protein-Tyrosine Kinases
Saponins
Antineoplastic Agents
Phytogenic
Molecular biology
Cyclin-Dependent Kinases
Tongue Neoplasms
DNA-Binding Proteins
G2 Phase Cell Cycle Checkpoints
030104 developmental biology
Cyclin E2
030220 oncology & carcinogenesis
S Phase Cell Cycle Checkpoints
Carcinoma
Squamous Cell
biology.protein
Cyclin A1
Poly(ADP-ribose) Polymerases
Tumor Suppressor Protein p53
Melanthiaceae
Transcription Factors
Zdroj: Tumor Biology. 37:14863-14872
ISSN: 1423-0380
1010-4283
Popis: 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.
Databáze: OpenAIRE
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