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BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity
BACKGROUND: Multiple myeloma (MM) is a rare haematological disorder with few therapeutic options. BIBR1532, a telomerase inhibitor, is widely used in cancer treatment and has promising outcomes. In this study, we investigated the efficacy and mechanism of action of BIBR1532 in MM. METHODS: K562 and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638922/ https://www.ncbi.nlm.nih.gov/pubmed/37953768 http://dx.doi.org/10.7717/peerj.16404 |
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author | Zhang, Yuefeng Yang, Xinxin Zhou, Hangqun Yao, Guoli Zhou, Li Qian, Chunyan |
author_facet | Zhang, Yuefeng Yang, Xinxin Zhou, Hangqun Yao, Guoli Zhou, Li Qian, Chunyan |
author_sort | Zhang, Yuefeng |
collection | PubMed |
description | BACKGROUND: Multiple myeloma (MM) is a rare haematological disorder with few therapeutic options. BIBR1532, a telomerase inhibitor, is widely used in cancer treatment and has promising outcomes. In this study, we investigated the efficacy and mechanism of action of BIBR1532 in MM. METHODS: K562 and MEG-01 cells were cultured with BIBR1532 at different concentrations. After 24 and 48 h, cell survival was analyzed. Next, these cells were cultured with 25 and 50 µM BIBR1532 for 48 h, then, cell proliferation, apoptosis, and the expression of the telomerase activity related markers were tested by 5-Ethynyl-2′-deoxyuridine (EdU) staining, flow cytometric analysis, western blot and quantitative real-time PCR (qRT-PCR), respectively. Expression of Bcl-xL, Bad, Survivin, phosphorylation of PI3K, AKT, mTOR, ERK1/2, and MAPK were tested via western blotting. Further experiments were conducted to evaluate the synergistic effects of BIBR1532 and doxorubicin (Dox) or bortezomib (Bor). RESULTS: BIBR1532 inhibited K562 and MEG-01 cell survival in a dose- and time-dependent manner. In addition, BIBR1532 hindered cell proliferation while promoting apoptosis, and this effect was enhanced by increasing the BIBR1532 concentration. Moreover, BIBR1532 inhibited TERT and c-MYC expression, PI3K, AKT, mTOR phosphorylation, and facilitated ERK1/2 and MAPK phosphorylation. Additionally, BIBR1532 combined with Dox or Bor showed synergistic effects in MM treatment. CONCLUSION: BIBR1532 inhibits proliferation and promotes apoptosis in MM cells by inhibiting telomerase activity. Additionally, BIBR1532 combined with Dox or Bor exhibited synergistic effects, indicating that BIBR1532 may be a novel medicine for the treatment of MM. |
format | Online Article Text |
id | pubmed-10638922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106389222023-11-11 BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity Zhang, Yuefeng Yang, Xinxin Zhou, Hangqun Yao, Guoli Zhou, Li Qian, Chunyan PeerJ Biochemistry BACKGROUND: Multiple myeloma (MM) is a rare haematological disorder with few therapeutic options. BIBR1532, a telomerase inhibitor, is widely used in cancer treatment and has promising outcomes. In this study, we investigated the efficacy and mechanism of action of BIBR1532 in MM. METHODS: K562 and MEG-01 cells were cultured with BIBR1532 at different concentrations. After 24 and 48 h, cell survival was analyzed. Next, these cells were cultured with 25 and 50 µM BIBR1532 for 48 h, then, cell proliferation, apoptosis, and the expression of the telomerase activity related markers were tested by 5-Ethynyl-2′-deoxyuridine (EdU) staining, flow cytometric analysis, western blot and quantitative real-time PCR (qRT-PCR), respectively. Expression of Bcl-xL, Bad, Survivin, phosphorylation of PI3K, AKT, mTOR, ERK1/2, and MAPK were tested via western blotting. Further experiments were conducted to evaluate the synergistic effects of BIBR1532 and doxorubicin (Dox) or bortezomib (Bor). RESULTS: BIBR1532 inhibited K562 and MEG-01 cell survival in a dose- and time-dependent manner. In addition, BIBR1532 hindered cell proliferation while promoting apoptosis, and this effect was enhanced by increasing the BIBR1532 concentration. Moreover, BIBR1532 inhibited TERT and c-MYC expression, PI3K, AKT, mTOR phosphorylation, and facilitated ERK1/2 and MAPK phosphorylation. Additionally, BIBR1532 combined with Dox or Bor showed synergistic effects in MM treatment. CONCLUSION: BIBR1532 inhibits proliferation and promotes apoptosis in MM cells by inhibiting telomerase activity. Additionally, BIBR1532 combined with Dox or Bor exhibited synergistic effects, indicating that BIBR1532 may be a novel medicine for the treatment of MM. PeerJ Inc. 2023-11-08 /pmc/articles/PMC10638922/ /pubmed/37953768 http://dx.doi.org/10.7717/peerj.16404 Text en ©2023 Zhang 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, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Biochemistry Zhang, Yuefeng Yang, Xinxin Zhou, Hangqun Yao, Guoli Zhou, Li Qian, Chunyan BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity |
title | BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity |
title_full | BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity |
title_fullStr | BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity |
title_full_unstemmed | BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity |
title_short | BIBR1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity |
title_sort | bibr1532 inhibits proliferation and enhances apoptosis in multiple myeloma cells by reducing telomerase activity |
topic | Biochemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10638922/ https://www.ncbi.nlm.nih.gov/pubmed/37953768 http://dx.doi.org/10.7717/peerj.16404 |
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