PubMed:10656873 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/10656873","sourcedb":"PubMed","sourceid":"10656873","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/10656873","text":"beta-lapachone induces cell cycle arrest and apoptosis in human colon cancer cells.\nBACKGROUND: 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.\nMATERIALS AND METHODS: 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.\nRESULTS: 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.\nCONCLUSIONS: 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.","tracks":[{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":102,"end":115},"obj":"HP_0003003"},{"id":"T2","span":{"begin":102,"end":115},"obj":"HP_0100273"},{"id":"T3","span":{"begin":108,"end":115},"obj":"HP_0002664"},{"id":"T4","span":{"begin":160,"end":166},"obj":"HP_0002664"},{"id":"T5","span":{"begin":322,"end":334},"obj":"HP_0003003"},{"id":"T6","span":{"begin":322,"end":334},"obj":"HP_0100273"},{"id":"T7","span":{"begin":328,"end":334},"obj":"HP_0002664"},{"id":"T8","span":{"begin":474,"end":482},"obj":"HP_0001909"},{"id":"T9","span":{"begin":487,"end":502},"obj":"HP_0012125"},{"id":"T10","span":{"begin":496,"end":502},"obj":"HP_0002664"},{"id":"T11","span":{"begin":600,"end":612},"obj":"HP_0003003"},{"id":"T12","span":{"begin":600,"end":612},"obj":"HP_0100273"},{"id":"T13","span":{"begin":606,"end":612},"obj":"HP_0002664"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"},{"subj":"T3","pred":"source","obj":"PubmedHPO"},{"subj":"T4","pred":"source","obj":"PubmedHPO"},{"subj":"T5","pred":"source","obj":"PubmedHPO"},{"subj":"T6","pred":"source","obj":"PubmedHPO"},{"subj":"T7","pred":"source","obj":"PubmedHPO"},{"subj":"T8","pred":"source","obj":"PubmedHPO"},{"subj":"T9","pred":"source","obj":"PubmedHPO"},{"subj":"T10","pred":"source","obj":"PubmedHPO"},{"subj":"T11","pred":"source","obj":"PubmedHPO"},{"subj":"T12","pred":"source","obj":"PubmedHPO"},{"subj":"T13","pred":"source","obj":"PubmedHPO"}]},{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":191,"end":194},"obj":"gene:7157"},{"id":"T1","span":{"begin":160,"end":166},"obj":"disease:C0006826"},{"id":"T2","span":{"begin":191,"end":194},"obj":"gene:7157"},{"id":"T3","span":{"begin":160,"end":166},"obj":"disease:C1306459"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"},{"subj":"T2","pred":"source","obj":"DisGeNET"},{"subj":"T3","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"10656873-2#97#100#gene7157","span":{"begin":354,"end":357},"obj":"gene7157"},{"id":"10656873-2#203#225#diseaseC0023487","span":{"begin":460,"end":482},"obj":"diseaseC0023487"},{"id":"10656873-2#203#225#diseaseC2745900","span":{"begin":460,"end":482},"obj":"diseaseC2745900"},{"id":"10656873-2#230#245#diseaseC0376358","span":{"begin":487,"end":502},"obj":"diseaseC0376358"},{"id":"10656873-2#230#245#diseaseC0600139","span":{"begin":487,"end":502},"obj":"diseaseC0600139"}],"relations":[{"id":"97#100#gene7157203#225#diseaseC0023487","pred":"associated_with","subj":"10656873-2#97#100#gene7157","obj":"10656873-2#203#225#diseaseC0023487"},{"id":"97#100#gene7157203#225#diseaseC2745900","pred":"associated_with","subj":"10656873-2#97#100#gene7157","obj":"10656873-2#203#225#diseaseC2745900"},{"id":"97#100#gene7157230#245#diseaseC0376358","pred":"associated_with","subj":"10656873-2#97#100#gene7157","obj":"10656873-2#230#245#diseaseC0376358"},{"id":"97#100#gene7157230#245#diseaseC0600139","pred":"associated_with","subj":"10656873-2#97#100#gene7157","obj":"10656873-2#230#245#diseaseC0600139"}],"attributes":[{"subj":"10656873-2#97#100#gene7157","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10656873-2#203#225#diseaseC0023487","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10656873-2#203#225#diseaseC2745900","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10656873-2#230#245#diseaseC0376358","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"10656873-2#230#245#diseaseC0600139","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":96,"end":619},"obj":"BACKGROUND"},{"id":"T2","span":{"begin":643,"end":1031},"obj":"METHODS"},{"id":"T3","span":{"begin":1041,"end":2009},"obj":"RESULTS"},{"id":"T4","span":{"begin":2023,"end":2324},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T4","pred":"source","obj":"PubMed_Structured_Abstracts"}]},{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":64,"end":76},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":310,"end":313},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":322,"end":334},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T8","span":{"begin":460,"end":482},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T9","span":{"begin":487,"end":502},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T10","span":{"begin":600,"end":612},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T13","span":{"begin":657,"end":669},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T16","span":{"begin":1092,"end":1101},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T17","span":{"begin":1231,"end":1246},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T18","span":{"begin":2087,"end":2099},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T21","span":{"begin":2266,"end":2269},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0002032"},{"id":"A2","pred":"mondo_id","subj":"T1","obj":"0005575"},{"id":"A3","pred":"mondo_id","subj":"T1","obj":"0021063"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0012833"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0002032"},{"id":"A6","pred":"mondo_id","subj":"T5","obj":"0005575"},{"id":"A7","pred":"mondo_id","subj":"T5","obj":"0021063"},{"id":"A8","pred":"mondo_id","subj":"T8","obj":"0012883"},{"id":"A9","pred":"mondo_id","subj":"T9","obj":"0008315"},{"id":"A10","pred":"mondo_id","subj":"T10","obj":"0002032"},{"id":"A11","pred":"mondo_id","subj":"T10","obj":"0005575"},{"id":"A12","pred":"mondo_id","subj":"T10","obj":"0021063"},{"id":"A13","pred":"mondo_id","subj":"T13","obj":"0002032"},{"id":"A14","pred":"mondo_id","subj":"T13","obj":"0005575"},{"id":"A15","pred":"mondo_id","subj":"T13","obj":"0021063"},{"id":"A16","pred":"mondo_id","subj":"T16","obj":"0000605"},{"id":"A17","pred":"mondo_id","subj":"T17","obj":"0008315"},{"id":"A18","pred":"mondo_id","subj":"T18","obj":"0002032"},{"id":"A19","pred":"mondo_id","subj":"T18","obj":"0005575"},{"id":"A20","pred":"mondo_id","subj":"T18","obj":"0021063"},{"id":"A21","pred":"mondo_id","subj":"T21","obj":"0012833"},{"subj":"T1","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T4","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T5","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T8","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T9","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T10","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T13","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T16","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T17","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T18","pred":"source","obj":"PMID_GLOBAL"},{"subj":"T21","pred":"source","obj":"PMID_GLOBAL"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubmedHPO","color":"#b693ec","default":true},{"id":"DisGeNET","color":"#93ec9c"},{"id":"DisGeNET5_gene_disease","color":"#ec93a4"},{"id":"PubMed_Structured_Abstracts","color":"#93beec"},{"id":"PMID_GLOBAL","color":"#d8ec93"}]}]}}