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Bafilomycin induces the p21-mediated growth inhibition of cancer cells under hypoxic conditions by expressing hypoxia-inducible factor-1alpha
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lim, Ji-Hong | - |
dc.contributor.author | Park, Jong-Wan | - |
dc.contributor.author | Kim, Myung-Suk | - |
dc.contributor.author | Park, Sang-Ki | - |
dc.contributor.author | Johnson, Randall S. | - |
dc.contributor.author | Chun, Yang-Sook | - |
dc.date.accessioned | 2009-12-29T06:58:13Z | - |
dc.date.available | 2009-12-29T06:58:13Z | - |
dc.date.issued | 2006 | - |
dc.identifier.citation | Mol Pharmacol 70:1856-1865 | en |
dc.identifier.issn | 0026-895X (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16940187 | - |
dc.identifier.uri | https://hdl.handle.net/10371/23141 | - |
dc.description.abstract | Bafilomycin A1, a macrolide antibiotic isolated from Streptomyces species, has been used as an inhibitor of vacuolar H(+) ATPase (V-ATPase). Bafilomycin has been also evaluated as a potential anticancer agent because it inhibits cell proliferation and tumor growth. Although these anticancer effects of bafilomycin are considered to be attributable to the intracellular acidosis by V-ATPase inhibition, the exact mechanism remains unclear. In the present study, we tested the possibility that bafilomycin targets a tumor-promoting factor, hypoxia-inducible factor-1alpha (HIF-1alpha). Bafilomycin A1 and its analog, concanamycin A, were found to up-regulate HIF-1alpha in eight human cancer cell-lines, and this effect is attributed to inhibited degradation of HIF-1alpha protein. Furthermore, the HIF-1alpha induction by bafilomycin was augmented by hypoxia, which caused a robust induction of p21 and cell cycle arrest in cancer cells. The cell cycle inhibition was shown only in cancer cells expressing both HIF-1alpha and p21. In HIF-1alpha(+/+) or HIF-1alpha(-/-) fibrosarcomas grafted in nude mice, bafilomycin showed the HIF-1alpha-dependent anticancer effect. Based on these results, the exorbitant expression of HIF-1alpha is likely to contribute to the anticancer action of bafilomycin. | en |
dc.language.iso | en | en |
dc.publisher | American Society for Pharmacology and Experimental Therapeutics (ASPET) | en |
dc.subject | Animals | en |
dc.subject | Antineoplastic Agents/*pharmacology | en |
dc.subject | Blotting, Western | en |
dc.subject | Cell Cycle/drug effects | en |
dc.subject | Cell Division/*drug effects | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Cyclin-Dependent Kinase Inhibitor p21/biosynthesis | en |
dc.subject | Humans | en |
dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis | en |
dc.subject | Immunoprecipitation | en |
dc.subject | In Situ Nick-End Labeling | en |
dc.subject | Macrolides/*pharmacology | en |
dc.subject | Mice | en |
dc.subject | Mice, Nude | en |
dc.subject | Reverse Transcriptase Polymerase Chain Reaction | en |
dc.subject | Cell Hypoxia | - |
dc.title | Bafilomycin induces the p21-mediated growth inhibition of cancer cells under hypoxic conditions by expressing hypoxia-inducible factor-1alpha | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 임지홍 | - |
dc.contributor.AlternativeAuthor | 박종완 | - |
dc.contributor.AlternativeAuthor | 김명석 | - |
dc.contributor.AlternativeAuthor | 박상기 | - |
dc.contributor.AlternativeAuthor | 전양숙 | - |
dc.identifier.doi | 10.1124/mol.106.028076 | - |
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