Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yuanjiao, Qian, Jiacheng, Jiang, Mingmei, Yang, Shu, Zhou, Lianxin, Zhang, Qin, Lin, Liping, Yang, Ye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
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
_version_ 1785113529043386368
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
work_keys_str_mv AT zhangyuanjiao lte2inducescellapoptosisinmultiplemyelomabysuppressingaktphosphorylationatthr308andser473
AT qianjiacheng lte2inducescellapoptosisinmultiplemyelomabysuppressingaktphosphorylationatthr308andser473
AT jiangmingmei lte2inducescellapoptosisinmultiplemyelomabysuppressingaktphosphorylationatthr308andser473
AT yangshu lte2inducescellapoptosisinmultiplemyelomabysuppressingaktphosphorylationatthr308andser473
AT zhoulianxin lte2inducescellapoptosisinmultiplemyelomabysuppressingaktphosphorylationatthr308andser473
AT zhangqin lte2inducescellapoptosisinmultiplemyelomabysuppressingaktphosphorylationatthr308andser473
AT linliping lte2inducescellapoptosisinmultiplemyelomabysuppressingaktphosphorylationatthr308andser473
AT yangye lte2inducescellapoptosisinmultiplemyelomabysuppressingaktphosphorylationatthr308andser473