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Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling

Multiple myeloma (MM) is a hematological cancer causing from accumulated abnormal plasma cells. STAT3 overexpression in MM appears to be mediated by a variety of factors, and it may be associated with an adverse prognosis and play a role in microenvironment-dependent treatment resistance. Unfortunat...

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Autores principales: Heo, Sook-Kyoung, Noh, Eui-Kyu, Seo, Hye Jin, Lee, Yoo Jin, Koh, SuJin, Min, Young Joo, Choi, Yunsuk, Jo, Jae-Cheol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9064077/
https://www.ncbi.nlm.nih.gov/pubmed/35503759
http://dx.doi.org/10.1371/journal.pone.0265958
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author Heo, Sook-Kyoung
Noh, Eui-Kyu
Seo, Hye Jin
Lee, Yoo Jin
Koh, SuJin
Min, Young Joo
Choi, Yunsuk
Jo, Jae-Cheol
author_facet Heo, Sook-Kyoung
Noh, Eui-Kyu
Seo, Hye Jin
Lee, Yoo Jin
Koh, SuJin
Min, Young Joo
Choi, Yunsuk
Jo, Jae-Cheol
author_sort Heo, Sook-Kyoung
collection PubMed
description Multiple myeloma (MM) is a hematological cancer causing from accumulated abnormal plasma cells. STAT3 overexpression in MM appears to be mediated by a variety of factors, and it may be associated with an adverse prognosis and play a role in microenvironment-dependent treatment resistance. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM. Radotinib is a novel anti-cancer drug, currently approved in South Korea for the treatment of chronic myeloid leukemia patients. It is an oral, multitargeted inhibitor of receptor tyrosine kinases, including BCR-ABL, c-KIT, PDGFR, and Src family kinases. However, little is known about the effects of radotinib on multiple myeloma cells. However, little is known about the effects of radotinib on multiple myeloma cells. But even tinip almost not known about the impact of multiple myeloma cells. Moreover, nothing is known about how it affects STAT3 and JAK2. In this study, we analyzed the effect of radotinib on multiple myeloma cells. Herein, Moreover, nothing is known about how it. Moreover, not all is known about how the affects STAT3 and JAK2. We investigated the effect of radotinib on the STAT3 signaling pathway in MM cells, including several MM cell lines and mouse models. So we investigated the effect of radotinib on MM cells, including several MM cell lines and mouse models. Interestingly, radotinib induced apoptosis, and inhibited cell proliferation in MM cells including RPMI-8226, MM.1S, U266B1, and IM-9 cells. Moreover, radotinib treatment significantly increased the number Annexin V-positive cells and G0/G1-phase cells. In addition, radotinib treatment in various MM cells strongly suppressed the activity and expression of STAT3 and JAK2 proteins. We also observed that diverse proteins related to the STAT3 signaling pathway, including c-Myc, Bcl-xL, Mcl-1, cyclin D1 and cyclin D3, were powerfully inhibited by radotinib treatment in MM cells. Furthermore, radotinib significantly suppressed MM cell growth in a xenograft animal model using IM-9 cells. In conclusion, radotinib may play an important role as a candidate agent for MM treatment.
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spelling pubmed-90640772022-05-04 Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling Heo, Sook-Kyoung Noh, Eui-Kyu Seo, Hye Jin Lee, Yoo Jin Koh, SuJin Min, Young Joo Choi, Yunsuk Jo, Jae-Cheol PLoS One Research Article Multiple myeloma (MM) is a hematological cancer causing from accumulated abnormal plasma cells. STAT3 overexpression in MM appears to be mediated by a variety of factors, and it may be associated with an adverse prognosis and play a role in microenvironment-dependent treatment resistance. Unfortunately, MM remains an incurable disease, as relapse is very common. Therefore, there is urgent need to develop new treatment options for MM. Radotinib is a novel anti-cancer drug, currently approved in South Korea for the treatment of chronic myeloid leukemia patients. It is an oral, multitargeted inhibitor of receptor tyrosine kinases, including BCR-ABL, c-KIT, PDGFR, and Src family kinases. However, little is known about the effects of radotinib on multiple myeloma cells. However, little is known about the effects of radotinib on multiple myeloma cells. But even tinip almost not known about the impact of multiple myeloma cells. Moreover, nothing is known about how it affects STAT3 and JAK2. In this study, we analyzed the effect of radotinib on multiple myeloma cells. Herein, Moreover, nothing is known about how it. Moreover, not all is known about how the affects STAT3 and JAK2. We investigated the effect of radotinib on the STAT3 signaling pathway in MM cells, including several MM cell lines and mouse models. So we investigated the effect of radotinib on MM cells, including several MM cell lines and mouse models. Interestingly, radotinib induced apoptosis, and inhibited cell proliferation in MM cells including RPMI-8226, MM.1S, U266B1, and IM-9 cells. Moreover, radotinib treatment significantly increased the number Annexin V-positive cells and G0/G1-phase cells. In addition, radotinib treatment in various MM cells strongly suppressed the activity and expression of STAT3 and JAK2 proteins. We also observed that diverse proteins related to the STAT3 signaling pathway, including c-Myc, Bcl-xL, Mcl-1, cyclin D1 and cyclin D3, were powerfully inhibited by radotinib treatment in MM cells. Furthermore, radotinib significantly suppressed MM cell growth in a xenograft animal model using IM-9 cells. In conclusion, radotinib may play an important role as a candidate agent for MM treatment. Public Library of Science 2022-05-03 /pmc/articles/PMC9064077/ /pubmed/35503759 http://dx.doi.org/10.1371/journal.pone.0265958 Text en © 2022 Heo et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Heo, Sook-Kyoung
Noh, Eui-Kyu
Seo, Hye Jin
Lee, Yoo Jin
Koh, SuJin
Min, Young Joo
Choi, Yunsuk
Jo, Jae-Cheol
Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling
title Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling
title_full Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling
title_fullStr Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling
title_full_unstemmed Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling
title_short Radotinib inhibits multiple myeloma cell proliferation via suppression of STAT3 signaling
title_sort radotinib inhibits multiple myeloma cell proliferation via suppression of stat3 signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9064077/
https://www.ncbi.nlm.nih.gov/pubmed/35503759
http://dx.doi.org/10.1371/journal.pone.0265958
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