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Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells

Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CP...

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Autores principales: Qu, Na, Qu, Junsheng, Huang, Na, Zhang, Kexin, Ye, Tongtong, Shi, Junfeng, Chen, Bing, Kan, Chengxia, Zhang, Jingwen, Han, Fang, Hou, Ningning, Sun, Xiaodong, Pan, Ruiyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800829/
https://www.ncbi.nlm.nih.gov/pubmed/36588732
http://dx.doi.org/10.3389/fphar.2022.1056687
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author Qu, Na
Qu, Junsheng
Huang, Na
Zhang, Kexin
Ye, Tongtong
Shi, Junfeng
Chen, Bing
Kan, Chengxia
Zhang, Jingwen
Han, Fang
Hou, Ningning
Sun, Xiaodong
Pan, Ruiyan
author_facet Qu, Na
Qu, Junsheng
Huang, Na
Zhang, Kexin
Ye, Tongtong
Shi, Junfeng
Chen, Bing
Kan, Chengxia
Zhang, Jingwen
Han, Fang
Hou, Ningning
Sun, Xiaodong
Pan, Ruiyan
author_sort Qu, Na
collection PubMed
description Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CPAP cells were treated with calycosin, then cell proliferation, apoptosis and invasiveness were measured by CCK8 assay, flow cytometry, wound healing and transwell invasion assay, respectively. The cells were also performed by whole transcriptome microarray bioinformatics analysis. Apoptosis and autophagy-related markers or proteins were measured by qRT-PCR or western blot. Sestrin2-mediated AMPK/mTOR pathways were determined by western blot. We found that calycosin inhibited migration and invasion of B-CPAP cells and induced apoptosis (Bax/Bcl-2) and autophagy (LC3II/I, Beclin1) of B-CPAP cells. Differential expressed genes were screened between the calycosin-treated cells and control (524 genes upregulated and 328 genes downregulated). The pathway enrichment suggested that the role of calycosin in B-CPAP cells is closely related to apoptosis-related genes and p70S6 Kinase. Transmission electron microscopy found an increase in autophagosomes in calycosin-treated cells. Sestrin2 in human PTC tissues and B-CPAP cells was lower than in normal thyroid tissues and cells. And the pharmacological effects of calycosin in PTC cells were related to Sestrin2 activation, increased p-AMPK and inhibited p-mTOR and p-p70S6Kinase; these alterations were reversed when silencing Sestrin2. In conclusion, calycosin has an inhibitory effect on PTC via promoting apoptosis and autophagy through the Sestrin2/AMPK/mTOR pathway.
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spelling pubmed-98008292022-12-31 Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells Qu, Na Qu, Junsheng Huang, Na Zhang, Kexin Ye, Tongtong Shi, Junfeng Chen, Bing Kan, Chengxia Zhang, Jingwen Han, Fang Hou, Ningning Sun, Xiaodong Pan, Ruiyan Front Pharmacol Pharmacology Calycosin, one of small molecules derived from astragalus, has anti-tumor effects in various tumors. However, the effects of calycosin on papillary thyroid cancer (PTC) remain unclear. This study aimed to explore the anti-tumor ability of calycosin on human PTC and its potential mechanisms. The B-CPAP cells were treated with calycosin, then cell proliferation, apoptosis and invasiveness were measured by CCK8 assay, flow cytometry, wound healing and transwell invasion assay, respectively. The cells were also performed by whole transcriptome microarray bioinformatics analysis. Apoptosis and autophagy-related markers or proteins were measured by qRT-PCR or western blot. Sestrin2-mediated AMPK/mTOR pathways were determined by western blot. We found that calycosin inhibited migration and invasion of B-CPAP cells and induced apoptosis (Bax/Bcl-2) and autophagy (LC3II/I, Beclin1) of B-CPAP cells. Differential expressed genes were screened between the calycosin-treated cells and control (524 genes upregulated and 328 genes downregulated). The pathway enrichment suggested that the role of calycosin in B-CPAP cells is closely related to apoptosis-related genes and p70S6 Kinase. Transmission electron microscopy found an increase in autophagosomes in calycosin-treated cells. Sestrin2 in human PTC tissues and B-CPAP cells was lower than in normal thyroid tissues and cells. And the pharmacological effects of calycosin in PTC cells were related to Sestrin2 activation, increased p-AMPK and inhibited p-mTOR and p-p70S6Kinase; these alterations were reversed when silencing Sestrin2. In conclusion, calycosin has an inhibitory effect on PTC via promoting apoptosis and autophagy through the Sestrin2/AMPK/mTOR pathway. Frontiers Media S.A. 2022-12-16 /pmc/articles/PMC9800829/ /pubmed/36588732 http://dx.doi.org/10.3389/fphar.2022.1056687 Text en Copyright © 2022 Qu, Qu, Huang, Zhang, Ye, Shi, Chen, Kan, Zhang, Han, Hou, Sun and Pan. 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
Qu, Na
Qu, Junsheng
Huang, Na
Zhang, Kexin
Ye, Tongtong
Shi, Junfeng
Chen, Bing
Kan, Chengxia
Zhang, Jingwen
Han, Fang
Hou, Ningning
Sun, Xiaodong
Pan, Ruiyan
Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells
title Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells
title_full Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells
title_fullStr Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells
title_full_unstemmed Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells
title_short Calycosin induces autophagy and apoptosis via Sestrin2/AMPK/mTOR in human papillary thyroid cancer cells
title_sort calycosin induces autophagy and apoptosis via sestrin2/ampk/mtor in human papillary thyroid cancer cells
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9800829/
https://www.ncbi.nlm.nih.gov/pubmed/36588732
http://dx.doi.org/10.3389/fphar.2022.1056687
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