Inhibition of HIF-1 alpha using a novel Iron facilitator LS5-81 and its anti-cancer activity in hepatocellular carcinoma
| Project/Area Number |
23701094
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Clinical oncology
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| Research Institution | Asahikawa Medical College |
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Principal Investigator |
TANAKA Hiroki 旭川医科大学, 医学部, 特任講師 (70596155)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | HIF-1alpha / 鉄 / HIF-1α / HIF-1 alpha |
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| Research Abstract |
Targeting HIF-1a has been of therapeutic interest. In normoxic conditions, HIF-1a is hydroxylated by prolylhydroxylases (PHDs), which require iron for its activity. The tumor suppressor protein VHL binds to the hydroxylated HIF-1a, which is then degraded by proteasomes. We focused on the degradation machinery of HIF-1a mediated by PHDs. In this study, we aimed to inhibit the expression of HIF-1a protein and growth of hepatocellular carcinoma (HCC) using the iron-facilitating activity of LS5-81. In the human HCC cell lines, a combination of LS5-81 and iron inhibited HIF-1a protein expression. A mutated HIF-1a protein, which has proline residues that were replaced with alanine and transfected into HEK293 cells, was not affected by the combination of LS5-81 and iron. Furthermore, LS5-81 inhibited tumor growth of mouse HCC models. These results indicate that LS5-81 inhibits HIF-1a expression through prolyl-hydroxylation of HIF-1a and might have a therapeutic effect in the treatment of HCC.
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Report
(4 results)
Research Products
(11 results)
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[Presentation] Glass J A novel iron facilitator LS081 inhibits HIF-1α protein expression and functions as an anticancer agent Podium presentation, Fourth Congress of the International BioIron Society (IBIS)2011
Author(s)
Tanaka H, Ikuta K, Hosoki T, Sasaki K, Nakamura M, Akutsu H, Torimoto Y, Kohgo Y, Li Z
Organizer
Biennial World Meeting 2011
Place of Presentation
Vncouver, BC, Canada
Related Report
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