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Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways

Baicalin, a flavonoid derivative, exerts antitumor activity in a variety of neoplasms. However, whether baicalin exerts antitumor effects on osteosarcoma cells remains to be elucidated. In this study, treatment with baicalin reduced the proliferation and invasive potential of osteosarcoma cells and...

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Autores principales: Pang, He, Wu, Tingrui, Peng, Zhonghua, Tan, Qichao, Peng, Xin, Zhan, Zeyu, Song, Lijun, Wei, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091934/
https://www.ncbi.nlm.nih.gov/pubmed/35573641
http://dx.doi.org/10.1016/j.jbo.2022.100415
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author Pang, He
Wu, Tingrui
Peng, Zhonghua
Tan, Qichao
Peng, Xin
Zhan, Zeyu
Song, Lijun
Wei, Bo
author_facet Pang, He
Wu, Tingrui
Peng, Zhonghua
Tan, Qichao
Peng, Xin
Zhan, Zeyu
Song, Lijun
Wei, Bo
author_sort Pang, He
collection PubMed
description Baicalin, a flavonoid derivative, exerts antitumor activity in a variety of neoplasms. However, whether baicalin exerts antitumor effects on osteosarcoma cells remains to be elucidated. In this study, treatment with baicalin reduced the proliferation and invasive potential of osteosarcoma cells and reduced the mitochondrial membrane potential, which eventually caused mitochondrial apoptosis. In addition, baicalin increased intercellular Ca(2+) and ROS concentrations. Baicalin-induced apoptosis was confirmed by enhanced Bax, cleaved caspase-3, and cleaved PARP levels and decreased Bcl-2 levels. The increase in LC3-II and p62 suggested that baicalin induced autophagosome formation but ultimately inhibited downstream autophagy. Moreover, apoptosis induced by baicalin was attenuated by the addition of 3-MA. Furthermore, we found that baicalin inhibited the PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways. Chelation of free Ca(2+) by BAPTA-AM also inhibited both apoptosis induction and ROS concentration changes. Finally, NAC pretreatment reversed baicalin treatment outcomes, including the increase in Ca(2+) concentration, induction of apoptosis and autophagy, and inhibition of the pathways. Molecular docking results indicated that baicalin might interact with the structural domain of PI3Kγ. Thus, baicalin may be considered a potential candidate for osteosarcoma treatment.
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spelling pubmed-90919342022-05-12 Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways Pang, He Wu, Tingrui Peng, Zhonghua Tan, Qichao Peng, Xin Zhan, Zeyu Song, Lijun Wei, Bo J Bone Oncol Research Paper Baicalin, a flavonoid derivative, exerts antitumor activity in a variety of neoplasms. However, whether baicalin exerts antitumor effects on osteosarcoma cells remains to be elucidated. In this study, treatment with baicalin reduced the proliferation and invasive potential of osteosarcoma cells and reduced the mitochondrial membrane potential, which eventually caused mitochondrial apoptosis. In addition, baicalin increased intercellular Ca(2+) and ROS concentrations. Baicalin-induced apoptosis was confirmed by enhanced Bax, cleaved caspase-3, and cleaved PARP levels and decreased Bcl-2 levels. The increase in LC3-II and p62 suggested that baicalin induced autophagosome formation but ultimately inhibited downstream autophagy. Moreover, apoptosis induced by baicalin was attenuated by the addition of 3-MA. Furthermore, we found that baicalin inhibited the PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways. Chelation of free Ca(2+) by BAPTA-AM also inhibited both apoptosis induction and ROS concentration changes. Finally, NAC pretreatment reversed baicalin treatment outcomes, including the increase in Ca(2+) concentration, induction of apoptosis and autophagy, and inhibition of the pathways. Molecular docking results indicated that baicalin might interact with the structural domain of PI3Kγ. Thus, baicalin may be considered a potential candidate for osteosarcoma treatment. Elsevier 2022-02-01 /pmc/articles/PMC9091934/ /pubmed/35573641 http://dx.doi.org/10.1016/j.jbo.2022.100415 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Paper
Pang, He
Wu, Tingrui
Peng, Zhonghua
Tan, Qichao
Peng, Xin
Zhan, Zeyu
Song, Lijun
Wei, Bo
Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways
title Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways
title_full Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways
title_fullStr Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways
title_full_unstemmed Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways
title_short Baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ROS to inhibit PI3K/Akt/mTOR, ERK1/2 and β-catenin signaling pathways
title_sort baicalin induces apoptosis and autophagy in human osteosarcoma cells by increasing ros to inhibit pi3k/akt/mtor, erk1/2 and β-catenin signaling pathways
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091934/
https://www.ncbi.nlm.nih.gov/pubmed/35573641
http://dx.doi.org/10.1016/j.jbo.2022.100415
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