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Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway

Colorectal cancer (CRC) is one of the most common malignancies currently. Despite advances in drug development, the survival and response rates in CRC patients are still poor. In our previous study, a library comprised of 1056 bioactive compounds was used for screening of drugs that could suppress C...

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Autores principales: Tan, Xiang‐Peng, He, Yan, Huang, Yun‐Na, Zheng, Can‐Can, Li, Jun‐Qi, Liu, Qin‐Wen, He, Ming‐Liang, Li, Bin, Xu, Wen‐Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554656/
https://www.ncbi.nlm.nih.gov/pubmed/34766155
http://dx.doi.org/10.1002/mco2.83
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author Tan, Xiang‐Peng
He, Yan
Huang, Yun‐Na
Zheng, Can‐Can
Li, Jun‐Qi
Liu, Qin‐Wen
He, Ming‐Liang
Li, Bin
Xu, Wen‐Wen
author_facet Tan, Xiang‐Peng
He, Yan
Huang, Yun‐Na
Zheng, Can‐Can
Li, Jun‐Qi
Liu, Qin‐Wen
He, Ming‐Liang
Li, Bin
Xu, Wen‐Wen
author_sort Tan, Xiang‐Peng
collection PubMed
description Colorectal cancer (CRC) is one of the most common malignancies currently. Despite advances in drug development, the survival and response rates in CRC patients are still poor. In our previous study, a library comprised of 1056 bioactive compounds was used for screening of drugs that could suppress CRC. Lomerizine 2HCl, which is an approved prophylactic drug for migraines, was selected for our studies. The results of in vitro and in vivo assays suggested that lomerizine 2HCl suppresses cell growth and promotes apoptosis in CRC cells. Moreover, lomerizine 2HCl inhibits cell migration and invasion of CRC. RNA sequencing analysis and Western blotting confirmed that lomerizine 2HCl can inhibit cell growth, migration, and invasion through PI3K/AKT/mTOR signaling pathway and induces protective autophagy in CRC. Meanwhile, autophagy inhibition by 3‐methyladenine (3‐MA) increases lomerizine 2HCl‐induced cell apoptosis. Taken together, these results imply that lomerizine 2HCl is a potential anticancer agent, and the combination of lomerizine 2HCl and autophagy inhibitors may serve as a novel strategy to increase the antitumor efficacy of agents in the treatment of CRC.
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spelling pubmed-85546562021-11-10 Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway Tan, Xiang‐Peng He, Yan Huang, Yun‐Na Zheng, Can‐Can Li, Jun‐Qi Liu, Qin‐Wen He, Ming‐Liang Li, Bin Xu, Wen‐Wen MedComm (2020) Original Articles Colorectal cancer (CRC) is one of the most common malignancies currently. Despite advances in drug development, the survival and response rates in CRC patients are still poor. In our previous study, a library comprised of 1056 bioactive compounds was used for screening of drugs that could suppress CRC. Lomerizine 2HCl, which is an approved prophylactic drug for migraines, was selected for our studies. The results of in vitro and in vivo assays suggested that lomerizine 2HCl suppresses cell growth and promotes apoptosis in CRC cells. Moreover, lomerizine 2HCl inhibits cell migration and invasion of CRC. RNA sequencing analysis and Western blotting confirmed that lomerizine 2HCl can inhibit cell growth, migration, and invasion through PI3K/AKT/mTOR signaling pathway and induces protective autophagy in CRC. Meanwhile, autophagy inhibition by 3‐methyladenine (3‐MA) increases lomerizine 2HCl‐induced cell apoptosis. Taken together, these results imply that lomerizine 2HCl is a potential anticancer agent, and the combination of lomerizine 2HCl and autophagy inhibitors may serve as a novel strategy to increase the antitumor efficacy of agents in the treatment of CRC. John Wiley and Sons Inc. 2021-07-15 /pmc/articles/PMC8554656/ /pubmed/34766155 http://dx.doi.org/10.1002/mco2.83 Text en © 2021 The Authors. MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Tan, Xiang‐Peng
He, Yan
Huang, Yun‐Na
Zheng, Can‐Can
Li, Jun‐Qi
Liu, Qin‐Wen
He, Ming‐Liang
Li, Bin
Xu, Wen‐Wen
Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway
title Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway
title_full Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway
title_fullStr Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway
title_full_unstemmed Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway
title_short Lomerizine 2HCl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the PI3K/Akt/mTOR signaling pathway
title_sort lomerizine 2hcl inhibits cell proliferation and induces protective autophagy in colorectal cancer via the pi3k/akt/mtor signaling pathway
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554656/
https://www.ncbi.nlm.nih.gov/pubmed/34766155
http://dx.doi.org/10.1002/mco2.83
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