| Item type |
学術雑誌論文 / Journal Article_02(1) |
| 公開日 |
2012-05-14 |
| タイトル |
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タイトル |
Iron facilitator LS081 reduces hypoxia-inducible factor-1α protein and functions as anticancer agent in hepatocellular carcinoma. |
|
言語 |
en |
| 言語 |
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|
言語 |
eng |
| 資源タイプ |
|
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資源タイプ |
journal article |
| 著者 |
田中, 宏樹
Zhen, Li
Katsuya, Ikuta
Lynda, Addo
Hiroaki, Akutsu
Masao, Nakamura
Katsunori, Sasaki
Takaaki, Ohtake
Mikihiro, Fujiya
Yoshihiro, Torimoto
Jonathan, Glass
Yutaka, Kohgo
|
| 書誌情報 |
Cancer Science
巻 103,
号 4,
p. 767-774,
発行日 2012-04-01
|
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1349-7006 |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
10.1111/j.1349-7006.2011.02192.x |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
22181812 |
| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Hypoxia inducible factor-1α (HIF-1α) has a central role in cellular oxygen-sensing, and its overexpression in many types of cancer is considered important in tumor progression. Thus, targeting HIF-1α production and activity has been of great therapeutic interest. In normoxic conditions, HIF-1α is hydroxylated by oxygen-dependent prolyl-hydroxylases, which require ferrous iron for its activity. The tumor suppressor protein von Hippel Lindau binds to the hydroxylated HIF-1α, which is then ubiquitinated and degraded by proteasomes. We focused on the physiological degradation machinery of HIF-1α mediated by prolyl hydroxylases. Previously, we identified a small molecule, LS081, that is capable of stimulating iron uptake into cells. In the present study, we aimed to inhibit the expression of HIF-1α protein and growth of hepatocellular carcinoma by using the iron-facilitating activity of LS081. In the human hepatocellular carcinoma cell lines Hep3B and HepG2, a combination of LS081 and ferric ammonium citrate (LS081/FeAC) inhibited HIF-1α protein expression but did not inhibit HIF-1α mRNA expression. A mutated HIF-1α protein, which has proline residues that were replaced with alanine and transfected into HEK293 cells, was not affected by the combination of LS081 and FeAC. Furthermore, the iron-facilitating activity of LS081 resulted in Hep3B and HepG2 growth inhibition in vitro and in vivo. These results indicate that the iron-facilitating activity of LS081 inhibits HIF-1α expression through prolyl-hydroxylation of HIF-1α and might have a therapeutic effect in the treatment of hepatocellular carcinoma. |
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言語 |
en |
| 注記 |
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内容記述タイプ |
Other |
|
注記 |
Author |
| 資源タイプ |
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内容記述タイプ |
Other |
|
資源タイプ |
text |
| 著者版フラグ |
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出版タイプ |
AM |
| フォーマット |
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内容記述タイプ |
Other |
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内容記述 |
application/pdf |
| ID(XooNIps) |
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22181812 |
| 閲覧数(XooNIps) |
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| ダウンロード数(XooNIps) |
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|
1053 |
4404.pdf (5.9 MB)
