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Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells
Background and Objectives: Natural products are necessary sources for drug discovery and have contributed to cancer chemotherapy over the past few decades. Furthermore, substances derived from plants have fewer side effects. Chrysophanol is an anthraquinone derivative that is isolated from rhubarb....
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864245/ https://www.ncbi.nlm.nih.gov/pubmed/36676666 http://dx.doi.org/10.3390/medicina59010042 |
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author | Park, Dan-Bi Park, Bong-Soo Kang, Hae-Mi Kim, Jung-Han Kim, In-Ryoung |
author_facet | Park, Dan-Bi Park, Bong-Soo Kang, Hae-Mi Kim, Jung-Han Kim, In-Ryoung |
author_sort | Park, Dan-Bi |
collection | PubMed |
description | Background and Objectives: Natural products are necessary sources for drug discovery and have contributed to cancer chemotherapy over the past few decades. Furthermore, substances derived from plants have fewer side effects. Chrysophanol is an anthraquinone derivative that is isolated from rhubarb. Although the anticancer effect of chrysophanol on several cancer cells has been reported, studies on the antitumor effect of chrysophanol on oral squamous-cell carcinoma (OSCC) cells have yet to be elucidated. Therefore, in this study, we investigated the anticancer effect of chrysophanol on OSCC cells (CAL-27 and Ca9-22) via apoptosis and autophagy, among the cell death pathways. Results: It was found that chrysophanol inhibited the growth and viability of CAL-27 and Ca9-22 and induced apoptosis through the intrinsic pathway. It was also found that chrysophanol activates autophagy-related factors (ATG5, beclin-1, and P62/SQSTM1) and LC3B conversion. That is, chrysophanol activated both apoptosis and autophagy. Here, we focused on the roles of chrysophanol-induced apoptosis and the autophagy pathway. When the autophagy inhibitor 3-MA and PI3K/Akt inhibitor were used to inhibit the autophagy induced by chrysophanol, it was confirmed that the rate of apoptosis significantly increased. Therefore, we confirmed that chrysophanol induces apoptosis and autophagy at the same time, and the induced autophagy plays a role in interfering with apoptosis processes. Conclusions: Therefore, the potential of chrysophanol as an excellent anticancer agent in OSCC was confirmed via this study. Furthermore, the combined treatment of drugs that can inhibit chrysophanol-induced autophagy is expected to have a tremendous synergistic effect in overcoming oral cancer. |
format | Online Article Text |
id | pubmed-9864245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98642452023-01-22 Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells Park, Dan-Bi Park, Bong-Soo Kang, Hae-Mi Kim, Jung-Han Kim, In-Ryoung Medicina (Kaunas) Article Background and Objectives: Natural products are necessary sources for drug discovery and have contributed to cancer chemotherapy over the past few decades. Furthermore, substances derived from plants have fewer side effects. Chrysophanol is an anthraquinone derivative that is isolated from rhubarb. Although the anticancer effect of chrysophanol on several cancer cells has been reported, studies on the antitumor effect of chrysophanol on oral squamous-cell carcinoma (OSCC) cells have yet to be elucidated. Therefore, in this study, we investigated the anticancer effect of chrysophanol on OSCC cells (CAL-27 and Ca9-22) via apoptosis and autophagy, among the cell death pathways. Results: It was found that chrysophanol inhibited the growth and viability of CAL-27 and Ca9-22 and induced apoptosis through the intrinsic pathway. It was also found that chrysophanol activates autophagy-related factors (ATG5, beclin-1, and P62/SQSTM1) and LC3B conversion. That is, chrysophanol activated both apoptosis and autophagy. Here, we focused on the roles of chrysophanol-induced apoptosis and the autophagy pathway. When the autophagy inhibitor 3-MA and PI3K/Akt inhibitor were used to inhibit the autophagy induced by chrysophanol, it was confirmed that the rate of apoptosis significantly increased. Therefore, we confirmed that chrysophanol induces apoptosis and autophagy at the same time, and the induced autophagy plays a role in interfering with apoptosis processes. Conclusions: Therefore, the potential of chrysophanol as an excellent anticancer agent in OSCC was confirmed via this study. Furthermore, the combined treatment of drugs that can inhibit chrysophanol-induced autophagy is expected to have a tremendous synergistic effect in overcoming oral cancer. MDPI 2022-12-26 /pmc/articles/PMC9864245/ /pubmed/36676666 http://dx.doi.org/10.3390/medicina59010042 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Park, Dan-Bi Park, Bong-Soo Kang, Hae-Mi Kim, Jung-Han Kim, In-Ryoung Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells |
title | Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells |
title_full | Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells |
title_fullStr | Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells |
title_full_unstemmed | Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells |
title_short | Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells |
title_sort | chrysophanol-induced autophagy disrupts apoptosis via the pi3k/akt/mtor pathway in oral squamous cell carcinoma cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864245/ https://www.ncbi.nlm.nih.gov/pubmed/36676666 http://dx.doi.org/10.3390/medicina59010042 |
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