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Luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines

The epidermal growth factor (EGFR) receptor is frequently overexpressed in glioblastoma multiforme IV (GBM). Increased expression of EGFR leads to increased proliferation, decreased apoptosis, and increased resistance to chemotherapeutic agents. A small molecule called erlotinib inhibits EGFR recept...

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Autores principales: Powe, Erika, Parschauer, Daniel, Istifan, Jessica, Lin, Stacy, Duan, Huanyun, Gryka, Rebecca, Jean-Louis, Denise, Tiwari, Amit K., Amos, Samson
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527275/
https://www.ncbi.nlm.nih.gov/pubmed/36199696
http://dx.doi.org/10.3389/fphar.2022.952169
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author Powe, Erika
Parschauer, Daniel
Istifan, Jessica
Lin, Stacy
Duan, Huanyun
Gryka, Rebecca
Jean-Louis, Denise
Tiwari, Amit K.
Amos, Samson
author_facet Powe, Erika
Parschauer, Daniel
Istifan, Jessica
Lin, Stacy
Duan, Huanyun
Gryka, Rebecca
Jean-Louis, Denise
Tiwari, Amit K.
Amos, Samson
author_sort Powe, Erika
collection PubMed
description The epidermal growth factor (EGFR) receptor is frequently overexpressed in glioblastoma multiforme IV (GBM). Increased expression of EGFR leads to increased proliferation, decreased apoptosis, and increased resistance to chemotherapeutic agents. A small molecule called erlotinib inhibits EGFR receptors by binding to their adenosine triphosphate (ATP) binding sites. It is FDA approved to treat a variety of EGFR-mediated cancers. Several clinical trials have explored a combination of erlotinib with other agents to treat glioblastoma since it is believed that erlotinib would benefit patients with GBM with EGFR mutations or expression. Luteolin, a natural flavonoid, inhibits cell growth and induces apoptosis in cancer cells. We investigated the combined effects of erlotinib and luteolin on proliferation and apoptosis on glioblastoma cell lines overexpressing EGFR or glioma cells expressing truncated EGFR (ΔEGFR). In a concentration-dependent fashion, the combination of luteolin and erlotinib reduced cell proliferation (p < 0.05) and induced apoptosis by cleaving PARP and increasing caspase expression. In addition, the combination of luteolin and erlotinib reduced the phosphorylation of downstream EGFR cell signaling molecules such as Akt, NF kappa B, and STAT3 in a concentration-dependent manner. These findings suggest that combining luteolin with erlotinib offers a potential treatment strategy for glioblastoma multiforme IV.
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spelling pubmed-95272752022-10-04 Luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines Powe, Erika Parschauer, Daniel Istifan, Jessica Lin, Stacy Duan, Huanyun Gryka, Rebecca Jean-Louis, Denise Tiwari, Amit K. Amos, Samson Front Pharmacol Pharmacology The epidermal growth factor (EGFR) receptor is frequently overexpressed in glioblastoma multiforme IV (GBM). Increased expression of EGFR leads to increased proliferation, decreased apoptosis, and increased resistance to chemotherapeutic agents. A small molecule called erlotinib inhibits EGFR receptors by binding to their adenosine triphosphate (ATP) binding sites. It is FDA approved to treat a variety of EGFR-mediated cancers. Several clinical trials have explored a combination of erlotinib with other agents to treat glioblastoma since it is believed that erlotinib would benefit patients with GBM with EGFR mutations or expression. Luteolin, a natural flavonoid, inhibits cell growth and induces apoptosis in cancer cells. We investigated the combined effects of erlotinib and luteolin on proliferation and apoptosis on glioblastoma cell lines overexpressing EGFR or glioma cells expressing truncated EGFR (ΔEGFR). In a concentration-dependent fashion, the combination of luteolin and erlotinib reduced cell proliferation (p < 0.05) and induced apoptosis by cleaving PARP and increasing caspase expression. In addition, the combination of luteolin and erlotinib reduced the phosphorylation of downstream EGFR cell signaling molecules such as Akt, NF kappa B, and STAT3 in a concentration-dependent manner. These findings suggest that combining luteolin with erlotinib offers a potential treatment strategy for glioblastoma multiforme IV. Frontiers Media S.A. 2022-09-19 /pmc/articles/PMC9527275/ /pubmed/36199696 http://dx.doi.org/10.3389/fphar.2022.952169 Text en Copyright © 2022 Powe, Parschauer, Istifan, Lin, Duan, Gryka, Jean-Louis, Tiwari and Amos. 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 Pharmacology
Powe, Erika
Parschauer, Daniel
Istifan, Jessica
Lin, Stacy
Duan, Huanyun
Gryka, Rebecca
Jean-Louis, Denise
Tiwari, Amit K.
Amos, Samson
Luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines
title Luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines
title_full Luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines
title_fullStr Luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines
title_full_unstemmed Luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines
title_short Luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines
title_sort luteolin enhances erlotinib’s cell proliferation inhibitory and apoptotic effects in glioblastoma cell lines
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9527275/
https://www.ncbi.nlm.nih.gov/pubmed/36199696
http://dx.doi.org/10.3389/fphar.2022.952169
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