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Iron facilitator LS081 reduces hypoxia-inducible factor-1α protein and functions as anticancer agent in hepatocellular carcinoma.
https://asahikawa-med.repo.nii.ac.jp/records/3841
https://asahikawa-med.repo.nii.ac.jp/records/3841007884c6-9ecf-4fc8-a761-debd5da256b0
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
4404.pdf (5.9 MB)
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| Item type | 学術雑誌論文 / Journal Article_02(1) | |||||
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| 公開日 | 2012-05-14 | |||||
| タイトル | ||||||
| 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 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
田中, 宏樹
× 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 |
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| 書誌情報 |
Cancer Science 巻 103, 号 4, p. 767-774, 発行日 2012-04-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | EISSN | |||||
| 収録物識別子 | 1349-7006 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1111/j.1349-7006.2011.02192.x | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 22181812 | |||||
| 抄録 | ||||||
| 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. | |||||
| 言語 | en | |||||
| 注記 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Author | |||||
| 資源タイプ | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | text | |||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| ID(XooNIps) | ||||||
| 値 | 22181812 | |||||
| 閲覧数(XooNIps) | ||||||
| 値 | 1107 | |||||
| ダウンロード数(XooNIps) | ||||||
| 値 | 1053 | |||||
