| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-09-15 |
| タイトル |
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タイトル |
Antitumor effects of chloroquine/hydroxychloroquine mediated by inhibition of the NF-κB signaling pathway through abrogation of autophagic p47 degradation in adult T-cell leukemia/lymphoma cells |
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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 |
Fauzi, Yanuar Rahmat
Nakahata, Shingo
シャール, チルミ
Ichikawa, Tomonaga
Nueangphuet, Phawut
山口, 良二
Nakamura, Tatsufumi
下田, 和哉
森下, 和広
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| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Adult T-cell leukemia/lymphoma (ATLL) originates from human T-cell leukemia virus type 1 (HTLV-1) infection due to the activation of the nuclear factor-κB (NF-κB) signaling pathway to maintain proliferation and survival. An important mechanism of the activated NF-κB signaling pathway in ATLL is the activation of the macroautophagy (herafter referred to as autophagy in the remainder of this manuscript)-lysosomal degradation of p47 (NSFL1C), a negative regulator of the NF-κB pathway. Therefore, we considered the use of chloroquine (CQ) or hydroxychloroquine (HCQ) (CQ/HCQ) as an autophagy inhibitor to treat ATLL; these drugs were originally approved by the FDA as antimalarial drugs and have recently been used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE). In this paper, we determined the therapeutic efficacy of CQ/HCQ, as NF-κB inhibitors, in ATLL mediated by blockade of p47 degradation. Administration of CQ/HCQ to ATLL cell lines and primary ATLL cells induced cell growth inhibition in a dose-dependent manner, and the majority of cells underwent apoptosis after CQ administration. As to the molecular mechanism, autophagy was inhibited in CQ-treated ATLL cells, and activation of the NF-κB pathway was suppressed with the restoration of the p47 level. When the antitumor effect of CQ/HCQ was examined using immunodeficient mice transplanted with ATLL cell lines, CQ/HCQ significantly suppressed tumor growth and improved the survival rate in the ATLL xenograft mouse model. Importantly, HCQ selectively induced ATLL cell death in the ATLL xenograft mouse model at the dose used to treat SLE. Taken together, our results suggest that the inhibition of autophagy by CQ/HCQ may become a novel and effective strategy for the treatment of ATLL. |
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言語 |
en |
| 内容記述 |
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内容記述タイプ |
Other |
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内容記述 |
Citation: Fauzi YR, Nakahata S, Chilmi S, Ichikawa T, Nueangphuet P, Yamaguchi R, et al. (2021) Antitumor effects of chloroquine/hydroxychloroquine mediated by inhibition of the NF-κB signaling pathway through abrogation of autophagic p47 degradation in adult T-cell leukemia/lymphoma cells. PLoS ONE 16(8): e0256320. https://doi.org/10.1371/journal.pone.0256320 |
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言語 |
en |
| 書誌情報 |
en : PLOS ONE
巻 16,
号 8,
p. e0256320,
発行日 2021-05-18
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| 出版者 |
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出版者 |
PLOS |
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言語 |
en |
| 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 |
https://doi.org/10.1371/journal.pone.0256320 |
| 権利 |
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言語 |
en |
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権利情報 |
© 2021 Fauzi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| 著者版フラグ |
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出版タイプ |
VoR |
本文 (1.7 MB)
