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Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells
T‐cell acute lymphoblastic leukemia (T‐ALL) is one of the most frequently occurring cancers in children and is associated with a poor prognosis. Here, we performed large‐scale screening of natural compound libraries to identify potential drugs against T‐ALL. We identified three low‐molecular‐weight...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551604/ https://www.ncbi.nlm.nih.gov/pubmed/37522388 http://dx.doi.org/10.1111/cas.15918 |
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author | Miyashita, Kazuya Yagi, Takuya Kagaya, Noritaka Takechi, Azusa Nakata, Chihiro Kanda, Risa Nuriya, Hideko Tanegashima, Kosuke Hoyano, Shota Seki, Fumiya Yoshida, Chihiro Hachiro, Yoshifumi Higashi, Tomoya Kitada, Nobuo Toya, Takashi Kobayashi, Takeshi Najima, Yuho Goyama, Susumu Maki, Shojiro A. Kitamura, Toshio Doki, Noriko Shin‐ya, Kazuo Hara, Takahiko |
author_facet | Miyashita, Kazuya Yagi, Takuya Kagaya, Noritaka Takechi, Azusa Nakata, Chihiro Kanda, Risa Nuriya, Hideko Tanegashima, Kosuke Hoyano, Shota Seki, Fumiya Yoshida, Chihiro Hachiro, Yoshifumi Higashi, Tomoya Kitada, Nobuo Toya, Takashi Kobayashi, Takeshi Najima, Yuho Goyama, Susumu Maki, Shojiro A. Kitamura, Toshio Doki, Noriko Shin‐ya, Kazuo Hara, Takahiko |
author_sort | Miyashita, Kazuya |
collection | PubMed |
description | T‐cell acute lymphoblastic leukemia (T‐ALL) is one of the most frequently occurring cancers in children and is associated with a poor prognosis. Here, we performed large‐scale screening of natural compound libraries to identify potential drugs against T‐ALL. We identified three low‐molecular‐weight compounds (auxarconjugatin‐B, rumbrin, and lavendamycin) that inhibited the proliferation of the T‐ALL cell line CCRF‐CEM, but not that of the B lymphoma cell line Raji in a low concentration range. Among them, auxarconjugatin‐B and rumbrin commonly contained a polyenyl 3‐chloropyrrol in their chemical structure, therefore we chose auxarconjugatin‐B for further analyses. Auxarconjugatin‐B suppressed the in vitro growth of five human T‐ALL cell lines and two T‐ALL patient‐derived cells, but not that of adult T‐cell leukemia patient‐derived cells. Cultured normal T cells were several‐fold resistant to auxarconjugatin‐B. Auxarconjugatin‐B and its synthetic analogue Ra#37 depolarized the mitochondrial membrane potential of CCRF‐CEM cells within 3 h of treatment. These compounds are promising seeds for developing novel anti‐T‐ALL drugs. |
format | Online Article Text |
id | pubmed-10551604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105516042023-10-06 Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells Miyashita, Kazuya Yagi, Takuya Kagaya, Noritaka Takechi, Azusa Nakata, Chihiro Kanda, Risa Nuriya, Hideko Tanegashima, Kosuke Hoyano, Shota Seki, Fumiya Yoshida, Chihiro Hachiro, Yoshifumi Higashi, Tomoya Kitada, Nobuo Toya, Takashi Kobayashi, Takeshi Najima, Yuho Goyama, Susumu Maki, Shojiro A. Kitamura, Toshio Doki, Noriko Shin‐ya, Kazuo Hara, Takahiko Cancer Sci ORIGINAL ARTICLES T‐cell acute lymphoblastic leukemia (T‐ALL) is one of the most frequently occurring cancers in children and is associated with a poor prognosis. Here, we performed large‐scale screening of natural compound libraries to identify potential drugs against T‐ALL. We identified three low‐molecular‐weight compounds (auxarconjugatin‐B, rumbrin, and lavendamycin) that inhibited the proliferation of the T‐ALL cell line CCRF‐CEM, but not that of the B lymphoma cell line Raji in a low concentration range. Among them, auxarconjugatin‐B and rumbrin commonly contained a polyenyl 3‐chloropyrrol in their chemical structure, therefore we chose auxarconjugatin‐B for further analyses. Auxarconjugatin‐B suppressed the in vitro growth of five human T‐ALL cell lines and two T‐ALL patient‐derived cells, but not that of adult T‐cell leukemia patient‐derived cells. Cultured normal T cells were several‐fold resistant to auxarconjugatin‐B. Auxarconjugatin‐B and its synthetic analogue Ra#37 depolarized the mitochondrial membrane potential of CCRF‐CEM cells within 3 h of treatment. These compounds are promising seeds for developing novel anti‐T‐ALL drugs. John Wiley and Sons Inc. 2023-07-31 /pmc/articles/PMC10551604/ /pubmed/37522388 http://dx.doi.org/10.1111/cas.15918 Text en © 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | ORIGINAL ARTICLES Miyashita, Kazuya Yagi, Takuya Kagaya, Noritaka Takechi, Azusa Nakata, Chihiro Kanda, Risa Nuriya, Hideko Tanegashima, Kosuke Hoyano, Shota Seki, Fumiya Yoshida, Chihiro Hachiro, Yoshifumi Higashi, Tomoya Kitada, Nobuo Toya, Takashi Kobayashi, Takeshi Najima, Yuho Goyama, Susumu Maki, Shojiro A. Kitamura, Toshio Doki, Noriko Shin‐ya, Kazuo Hara, Takahiko Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells |
title | Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells |
title_full | Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells |
title_fullStr | Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells |
title_full_unstemmed | Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells |
title_short | Identification of compounds that preferentially suppress the growth of T‐cell acute lymphoblastic leukemia‐derived cells |
title_sort | identification of compounds that preferentially suppress the growth of t‐cell acute lymphoblastic leukemia‐derived cells |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10551604/ https://www.ncbi.nlm.nih.gov/pubmed/37522388 http://dx.doi.org/10.1111/cas.15918 |
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