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Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling
BACKGROUND: Oridonin is a diterpenoid isolated from Rabdosia rubescens that has potent anticancer activity. This study set out to investigate the antitumor effects of oridonin in pancreatic carcinoma (PC) and their underlying mechanisms. METHODS: To investigate the antitumor effects of oridonin, we...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
AME Publishing Company
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339817/ https://www.ncbi.nlm.nih.gov/pubmed/34422996 http://dx.doi.org/10.21037/atm-21-2630 |
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author | Zhao, Xin Zhang, Qi Wang, Yuanyuan Li, Shipeng Yu, Xiangyang Wang, Botao Wang, Ximo |
author_facet | Zhao, Xin Zhang, Qi Wang, Yuanyuan Li, Shipeng Yu, Xiangyang Wang, Botao Wang, Ximo |
author_sort | Zhao, Xin |
collection | PubMed |
description | BACKGROUND: Oridonin is a diterpenoid isolated from Rabdosia rubescens that has potent anticancer activity. This study set out to investigate the antitumor effects of oridonin in pancreatic carcinoma (PC) and their underlying mechanisms. METHODS: To investigate the antitumor effects of oridonin, we developed an orthotopic C57BL/6 mouse model of PC. After successful establishment of the model, the mice were given a daily intraperitoneal injection of phosphate-buffered saline containing 0.1% dimethyl sulfoxide or oridonin for 2 weeks. In vitro experiments including MTT assay and flow cytometry were performed to examine cell viability and apoptosis. Panc-1 and Panc02 cells were transfected with a green fluorescent protein (GFP)-LC3 plasmid. After the cells had been treated with or without 20 μM oridonin and 10 μM 3-MA, the formation of GFP-LC3 puncta was detected by fluorescence microscopy. The levels of the autophagy-related proteins Beclin-1, LC3, and p62 were measured by western blotting. RESULTS: Oridonin inhibited the proliferation of PC cells and induced their apoptosis in vitro and in vivo. Treatment with oridonin also led to an increase in the quantity of LC3B II protein and upregulation of the p62 and Beclin-1 levels in PC cells. The effects of oridonin on PC cell proliferation, apoptosis, and autophagy were mediated via the simultaneous inhibition of the phosphoinositide 3-kinase pathway and activation of the c-Jun N-terminal kinase pathway. CONCLUSIONS: Our study is the first to confirm the antitumor and autophagy-activating effects of oridonin on PC cells. In light of these results, oridonin may be a promising therapeutic agent for PC. |
format | Online Article Text |
id | pubmed-8339817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | AME Publishing Company |
record_format | MEDLINE/PubMed |
spelling | pubmed-83398172021-08-20 Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling Zhao, Xin Zhang, Qi Wang, Yuanyuan Li, Shipeng Yu, Xiangyang Wang, Botao Wang, Ximo Ann Transl Med Original Article BACKGROUND: Oridonin is a diterpenoid isolated from Rabdosia rubescens that has potent anticancer activity. This study set out to investigate the antitumor effects of oridonin in pancreatic carcinoma (PC) and their underlying mechanisms. METHODS: To investigate the antitumor effects of oridonin, we developed an orthotopic C57BL/6 mouse model of PC. After successful establishment of the model, the mice were given a daily intraperitoneal injection of phosphate-buffered saline containing 0.1% dimethyl sulfoxide or oridonin for 2 weeks. In vitro experiments including MTT assay and flow cytometry were performed to examine cell viability and apoptosis. Panc-1 and Panc02 cells were transfected with a green fluorescent protein (GFP)-LC3 plasmid. After the cells had been treated with or without 20 μM oridonin and 10 μM 3-MA, the formation of GFP-LC3 puncta was detected by fluorescence microscopy. The levels of the autophagy-related proteins Beclin-1, LC3, and p62 were measured by western blotting. RESULTS: Oridonin inhibited the proliferation of PC cells and induced their apoptosis in vitro and in vivo. Treatment with oridonin also led to an increase in the quantity of LC3B II protein and upregulation of the p62 and Beclin-1 levels in PC cells. The effects of oridonin on PC cell proliferation, apoptosis, and autophagy were mediated via the simultaneous inhibition of the phosphoinositide 3-kinase pathway and activation of the c-Jun N-terminal kinase pathway. CONCLUSIONS: Our study is the first to confirm the antitumor and autophagy-activating effects of oridonin on PC cells. In light of these results, oridonin may be a promising therapeutic agent for PC. AME Publishing Company 2021-07 /pmc/articles/PMC8339817/ /pubmed/34422996 http://dx.doi.org/10.21037/atm-21-2630 Text en 2021 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Original Article Zhao, Xin Zhang, Qi Wang, Yuanyuan Li, Shipeng Yu, Xiangyang Wang, Botao Wang, Ximo Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling |
title | Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling |
title_full | Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling |
title_fullStr | Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling |
title_full_unstemmed | Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling |
title_short | Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling |
title_sort | oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-jun n-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339817/ https://www.ncbi.nlm.nih.gov/pubmed/34422996 http://dx.doi.org/10.21037/atm-21-2630 |
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