論文 - 詳細
| RRC ID | 58051 |
|---|---|
| 著者 | Tan YH, Shudo T, Yoshida T, Sugiyama Y, Si JY, Tsukano C, Takemoto Y, Kakizuka A. |
| タイトル | Ellagic acid, extracted from Sanguisorba officinalis, induces G1 arrest by modulating PTEN activity in B16F10 melanoma cells. |
| ジャーナル | Genes Cells |
| Abstract |
In Chinese medicine, herbal medicine is commonly used to treat individuals suffering from many types of diseases. We thus expected that some herbal medicines would contain promising compounds for cancer chemotherapy. Indeed, we found that Sanguisorba officinalis extracts strongly inhibit the growth of B16F10 melanoma cells, and we identified ellagic acid (EA) as the responsible ingredient. B16F10 cells treated with EA exhibited strong G1 arrest accompanied by accumulation of p53, followed by inactivation of AKT. Addition of a PTEN inhibitor, but not a p53 inhibitor, abrogated the EA-induced AKT inactivation and G1 arrest. The PTEN inhibitor also diminished EA-induced p53 accumulation. Furthermore, EA apparently increased the protein phosphatase activity of PTEN, as demonstrated by the reduced phosphorylation level of FAK, a protein substrate of PTEN. Furthermore, an in vitro PTEN phosphatase assay on PIP3 showed the direct modulation of PTEN activity by EA. These results suggest that EA functions as an allosteric modulator of PTEN, enhancing its protein phosphatase activity while inhibiting its lipid phosphatase activity. It is notable that a combination of EA and cisplatin, a widely used chemotherapy agent, dramatically enhanced cell death in B16F10 cells, suggesting a promising strategy in chemotherapy. |
| 巻・号 | 24(11) |
| ページ | 688-704 |
| 公開日 | 2019-11-1 |
| DOI | 10.1111/gtc.12719 |
| PMID | 31495058 |
| MeSH | Antineoplastic Agents / chemistry Antineoplastic Agents / pharmacology* Cell Death / drug effects Cell Line, Tumor Cisplatin / pharmacology Drug Therapy, Combination Drugs, Chinese Herbal / pharmacology Ellagic Acid / chemistry Ellagic Acid / isolation & purification Ellagic Acid / pharmacology* Focal Adhesion Kinase 1 G1 Phase Cell Cycle Checkpoints / drug effects* Herbal Medicine Humans Melanoma / drug therapy* PTEN Phosphohydrolase / drug effects PTEN Phosphohydrolase / metabolism* Phosphorylation Plant Extracts / pharmacology* Proto-Oncogene Proteins c-akt / metabolism Sanguisorba / chemistry* Signal Transduction / drug effects Tumor Suppressor Protein p53 / metabolism |
| IF | 1.655 |
| 引用数 | 1 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16F10(RCB2630) |