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LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473
Multiple myeloma (MM) is a highly heterogeneous hematological malignancy originating from B lymphocytes, with a high recurrence rate primarily due to drug resistance. 2-((1H-indol-3-yl)methyl)-3-((3-((1H-indol-3-yl)methyl)-1H-indol-2-yl)methyl)-1H-indole (LTe2), a tetrameric indole oligomer, possess...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539572/ https://www.ncbi.nlm.nih.gov/pubmed/37781194 http://dx.doi.org/10.3389/fonc.2023.1269670 |
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author | Zhang, Yuanjiao Qian, Jiacheng Jiang, Mingmei Yang, Shu Zhou, Lianxin Zhang, Qin Lin, Liping Yang, Ye |
author_facet | Zhang, Yuanjiao Qian, Jiacheng Jiang, Mingmei Yang, Shu Zhou, Lianxin Zhang, Qin Lin, Liping Yang, Ye |
author_sort | Zhang, Yuanjiao |
collection | PubMed |
description | Multiple myeloma (MM) is a highly heterogeneous hematological malignancy originating from B lymphocytes, with a high recurrence rate primarily due to drug resistance. 2-((1H-indol-3-yl)methyl)-3-((3-((1H-indol-3-yl)methyl)-1H-indol-2-yl)methyl)-1H-indole (LTe2), a tetrameric indole oligomer, possesses a wide range of anticancer activities through various mechanisms. Here, we aim to explore the anti-tumor efficiency and potential downstream targets of LTe2 in MM. Its bioactivity was assessed by employing MTT assays, flow cytometry, and the 5TMM3VT mouse model. Additionally, transcriptomic RNA-seq analysis and molecular dynamics (MD) experiments were conducted to elucidate the mechanism underlying LTe2 induced MM cell apoptosis. The results demonstrated that LTe2 significantly inhibited MM cell proliferation both in vitro and in vivo, and revealed that LTe2 exerts its effect by inhibiting the phosphorylation of AKT at the Thr308 and Ser473 sites. In summary, our findings highlight the potential of LTe2 as a novel candidate drug for MM treatment and provided a solid foundation for future clinical trials involving LTe2. |
format | Online Article Text |
id | pubmed-10539572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105395722023-09-30 LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473 Zhang, Yuanjiao Qian, Jiacheng Jiang, Mingmei Yang, Shu Zhou, Lianxin Zhang, Qin Lin, Liping Yang, Ye Front Oncol Oncology Multiple myeloma (MM) is a highly heterogeneous hematological malignancy originating from B lymphocytes, with a high recurrence rate primarily due to drug resistance. 2-((1H-indol-3-yl)methyl)-3-((3-((1H-indol-3-yl)methyl)-1H-indol-2-yl)methyl)-1H-indole (LTe2), a tetrameric indole oligomer, possesses a wide range of anticancer activities through various mechanisms. Here, we aim to explore the anti-tumor efficiency and potential downstream targets of LTe2 in MM. Its bioactivity was assessed by employing MTT assays, flow cytometry, and the 5TMM3VT mouse model. Additionally, transcriptomic RNA-seq analysis and molecular dynamics (MD) experiments were conducted to elucidate the mechanism underlying LTe2 induced MM cell apoptosis. The results demonstrated that LTe2 significantly inhibited MM cell proliferation both in vitro and in vivo, and revealed that LTe2 exerts its effect by inhibiting the phosphorylation of AKT at the Thr308 and Ser473 sites. In summary, our findings highlight the potential of LTe2 as a novel candidate drug for MM treatment and provided a solid foundation for future clinical trials involving LTe2. Frontiers Media S.A. 2023-09-14 /pmc/articles/PMC10539572/ /pubmed/37781194 http://dx.doi.org/10.3389/fonc.2023.1269670 Text en Copyright © 2023 Zhang, Qian, Jiang, Yang, Zhou, Zhang, Lin and Yang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhang, Yuanjiao Qian, Jiacheng Jiang, Mingmei Yang, Shu Zhou, Lianxin Zhang, Qin Lin, Liping Yang, Ye LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473 |
title | LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473 |
title_full | LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473 |
title_fullStr | LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473 |
title_full_unstemmed | LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473 |
title_short | LTe2 induces cell apoptosis in multiple myeloma by suppressing AKT phosphorylation at Thr308 and Ser473 |
title_sort | lte2 induces cell apoptosis in multiple myeloma by suppressing akt phosphorylation at thr308 and ser473 |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539572/ https://www.ncbi.nlm.nih.gov/pubmed/37781194 http://dx.doi.org/10.3389/fonc.2023.1269670 |
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