PubMed:10656873
Annnotations
PubMed_Structured_Abstracts
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 96-619 | BACKGROUND | denotes | Human colon cancers have a high frequency of p53 mutations, and cancer cells expressing mutant p53 tend to be resistant to current chemo- and radiation therapy. It is thus important to find therapeutic agents that can inhibit colon cancer cells with altered p53 status. beta-Lapachone, a novel topoisomerase inhibitor, has been shown to induce cell death in human promyelocytic leukemia and prostate cancer cells through a p53-independent pathway. Here we examined the effects of beta-lapachone on human colon cancer cells. |
| T2 | 643-1031 | METHODS | denotes | Several human colon cancer cell lines, SW480, SW620, and DLD1, with mutant or defective p53, were used. The antiproliferative effects of beta-lapachone were assessed by colony formation assays, cell cycle analysis, and apoptosis analysis, including annexin V staining and DNA laddering analysis. The effects on cell cycle and apoptosis regulatory proteins were examined by immunoblotting. |
| T3 | 1041-2009 | RESULTS | denotes | All three cell lines, SW480, SW620, and DLD1, were sensitive to beta-lapachone, with an IC(50) of 2 to 3 microM in colony formation assays, a finding similar to that previously reported for prostate cancer cells. However, these cells were arrested in different stages of S phase. At 24 hr post-treatment, beta-lapachone induced S-, late S/G2-, and early S-phase arrest in SW480, SW620, and DLD1 cells, respectively. The cell cycle alterations induced by beta-lapachone were congruous with changes in cell cycle regulatory proteins such as cyclin A, cyclin B1, cdc2, and cyclin D1. Moreover, beta-lapachone induced apoptosis, as demonstrated by annexin V staining, flow cytometric analysis of DNA content, and DNA laddering analysis. Furthermore, down-regulation of mutant p53 and induction of p27 in SW480 cells, and induction of pro-apoptotic protein Bax in DLD1 cells may be pertinent to the anti-proliferative and apoptotic effects of beta-lapachone on these cells. |
| T4 | 2023-2324 | CONCLUSIONS | denotes | beta-Lapachone induced cell cycle arrest and apoptosis in human colon cancer cells through a p53-independent pathway. For human colon cancers, which often contain p53 mutations, beta-lapachone may prove to be a promising anticancer agent that can target cancer cells, especially those with mutant p53. |
PMID_GLOBAL
| Id | Subject | Object | Predicate | Lexical cue | mondo_id |
|---|---|---|---|---|---|
| T1 | 64-76 | DiseaseOrPhenotypicFeature | denotes | colon cancer | 0002032|0005575|0021063 |
| T4 | 310-313 | DiseaseOrPhenotypicFeature | denotes | can | 0012833 |
| T5 | 322-334 | DiseaseOrPhenotypicFeature | denotes | colon cancer | 0002032|0005575|0021063 |
| T8 | 460-482 | DiseaseOrPhenotypicFeature | denotes | promyelocytic leukemia | 0012883 |
| T9 | 487-502 | DiseaseOrPhenotypicFeature | denotes | prostate cancer | 0008315 |
| T10 | 600-612 | DiseaseOrPhenotypicFeature | denotes | colon cancer | 0002032|0005575|0021063 |
| T13 | 657-669 | DiseaseOrPhenotypicFeature | denotes | colon cancer | 0002032|0005575|0021063 |
| T16 | 1092-1101 | DiseaseOrPhenotypicFeature | denotes | sensitive | 0000605 |
| T17 | 1231-1246 | DiseaseOrPhenotypicFeature | denotes | prostate cancer | 0008315 |
| T18 | 2087-2099 | DiseaseOrPhenotypicFeature | denotes | colon cancer | 0002032|0005575|0021063 |
| T21 | 2266-2269 | DiseaseOrPhenotypicFeature | denotes | can | 0012833 |
PubmedHPO
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T1 | 102-115 | HP_0003003 | denotes | colon cancers |
| T2 | 102-115 | HP_0100273 | denotes | colon cancers |
| T3 | 108-115 | HP_0002664 | denotes | cancers |
| T4 | 160-166 | HP_0002664 | denotes | cancer |
| T5 | 322-334 | HP_0003003 | denotes | colon cancer |
| T6 | 322-334 | HP_0100273 | denotes | colon cancer |
| T7 | 328-334 | HP_0002664 | denotes | cancer |
| T8 | 474-482 | HP_0001909 | denotes | leukemia |
| T9 | 487-502 | HP_0012125 | denotes | prostate cancer |
| T10 | 496-502 | HP_0002664 | denotes | cancer |
| T11 | 600-612 | HP_0003003 | denotes | colon cancer |
| T12 | 600-612 | HP_0100273 | denotes | colon cancer |
| T13 | 606-612 | HP_0002664 | denotes | cancer |
DisGeNET5_gene_disease
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| 10656873-2#97#100#gene7157 | 354-357 | gene7157 | denotes | p53 |
| 10656873-2#203#225#diseaseC0023487 | 460-482 | diseaseC0023487 | denotes | promyelocytic leukemia |
| 10656873-2#203#225#diseaseC2745900 | 460-482 | diseaseC2745900 | denotes | promyelocytic leukemia |
| 10656873-2#230#245#diseaseC0376358 | 487-502 | diseaseC0376358 | denotes | prostate cancer |
| 10656873-2#230#245#diseaseC0600139 | 487-502 | diseaseC0600139 | denotes | prostate cancer |
| 97#100#gene7157203#225#diseaseC0023487 | 10656873-2#97#100#gene7157 | 10656873-2#203#225#diseaseC0023487 | associated_with | p53,promyelocytic leukemia |
| 97#100#gene7157203#225#diseaseC2745900 | 10656873-2#97#100#gene7157 | 10656873-2#203#225#diseaseC2745900 | associated_with | p53,promyelocytic leukemia |
| 97#100#gene7157230#245#diseaseC0376358 | 10656873-2#97#100#gene7157 | 10656873-2#230#245#diseaseC0376358 | associated_with | p53,prostate cancer |
| 97#100#gene7157230#245#diseaseC0600139 | 10656873-2#97#100#gene7157 | 10656873-2#230#245#diseaseC0600139 | associated_with | p53,prostate cancer |
DisGeNET
| Id | Subject | Object | Predicate | Lexical cue |
|---|---|---|---|---|
| T0 | 191-194 | gene:7157 | denotes | p53 |
| T1 | 160-166 | disease:C0006826 | denotes | cancer |
| T2 | 191-194 | gene:7157 | denotes | p53 |
| T3 | 160-166 | disease:C1306459 | denotes | cancer |
| R1 | T0 | T1 | associated_with | p53,cancer |
| R2 | T2 | T3 | associated_with | p53,cancer |