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YC-1 induces S cell cycle arrest and apoptosis by activating checkpoint kinases
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yeo, Eun-Jin | - |
dc.contributor.author | Ryu, Ji-Hye | - |
dc.contributor.author | Chun, Yang-Sook | - |
dc.contributor.author | Cho, Young-Suk | - |
dc.contributor.author | Jang, In-Jin | - |
dc.contributor.author | Cho, HoSung | - |
dc.contributor.author | Kim, Jinho | - |
dc.contributor.author | Kim, Myung-Suk | - |
dc.contributor.author | Park, Jong-Wan | - |
dc.date.accessioned | 2010-01-04T05:06:02Z | - |
dc.date.available | 2010-01-04T05:06:02Z | - |
dc.date.issued | 2006-06-15 | - |
dc.identifier.citation | Cancer Res 2006;66:6345-52 | en |
dc.identifier.issn | 0008-5472 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16778212 | - |
dc.identifier.uri | https://hdl.handle.net/10371/24864 | - |
dc.description.abstract | Hypoxia-inducible factor-1alpha (HIF-1alpha) seems central to tumor growth and progression because it up-regulates genes essential for angiogenesis and the hypoxic adaptation of cancer cells, which is why HIF-1alpha inhibition is viewed as a cancer therapy strategy. Paradoxically, HIF-1alpha also leads to cell cycle arrest or the apoptosis of cancer cells. Thus, the possibility cannot be ruled out that HIF-1alpha inhibitors unlock cell cycle arrest under hypoxic conditions and prevent cell death, which would limit the anticancer effect of HIF-1alpha inhibitors. Previously, we reported on the development of YC-1 as an anticancer agent that inhibits HIF-1alpha. In the present study, we evaluated the effects of YC-1 on hypoxia-induced cell cycle arrest and cell death. It was found that YC-1 does not reverse the antiproliferative effect of hypoxia, but rather that it induces S-phase arrest and apoptosis at therapeutic concentrations that inhibit HIF-1alpha and tumor growth; however, YC-1 did not stimulate cyclic guanosine 3',5'-monophosphate production in this concentration range. It was also found that YC-1 activates the checkpoint kinase-mediated intra-S-phase checkpoint, independently of ataxia-telangiectasia mutated kinase or ataxia-telangiectasia mutated and Rad3-related kinase. These results imply that YC-1 does not promote the regrowth of hypoxic tumors because of its cell cycle arrest effect. Furthermore, YC-1 may induce the combined anticancer effects of HIF-1alpha inhibition and cell growth inhibition. | en |
dc.language.iso | en | - |
dc.publisher | American Association for Cancer Research | en |
dc.subject | Apoptosis/*drug effects/physiology | en |
dc.subject | Carcinoma, Hepatocellular/drug therapy/enzymology/pathology | en |
dc.subject | Cell Growth Processes/drug effects | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Enzyme Activation/drug effects | en |
dc.subject | Humans | en |
dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors | en |
dc.subject | Indazoles/pharmacokinetics/*pharmacology | en |
dc.subject | Liver Neoplasms/drug therapy/enzymology/pathology | en |
dc.subject | Protein Kinase Inhibitors/pharmacokinetics/pharmacology | en |
dc.subject | Protein Kinases/*metabolism | en |
dc.subject | Protein-Serine-Threonine Kinases/*metabolism | en |
dc.subject | S Phase/*drug effects/physiology | en |
dc.title | YC-1 induces S cell cycle arrest and apoptosis by activating checkpoint kinases | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 여은진 | - |
dc.contributor.AlternativeAuthor | 류지혜 | - |
dc.contributor.AlternativeAuthor | 전양숙 | - |
dc.contributor.AlternativeAuthor | 조영숙 | - |
dc.contributor.AlternativeAuthor | 장인진 | - |
dc.contributor.AlternativeAuthor | 조호성 | - |
dc.contributor.AlternativeAuthor | 김진호 | - |
dc.contributor.AlternativeAuthor | 김명석 | - |
dc.contributor.AlternativeAuthor | 박종완 | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-05-4460 | - |
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