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Article: Garcinone E triggers apoptosis and cell cycle arrest in human colorectal cancer cells by mediating a reactive oxygen species–dependent JNK signaling pathway

TitleGarcinone E triggers apoptosis and cell cycle arrest in human colorectal cancer cells by mediating a reactive oxygen species–dependent JNK signaling pathway
Authors
KeywordsApoptosis
Colorectal cancer
Reactive oxygen species
Xanthone
Issue Date29-Mar-2023
PublisherElsevier
Citation
Biomedicine and Pharmacotherapy, 2023, v. 162 How to Cite?
Abstract

Despite various therapeutic approaches, colorectal cancer is among the most fatal diseases globally. Hence, developing novel and more effective methods for colorectal cancer treatment is essential. Recently, reactive oxygen species (ROS)/JNK signaling pathway has been proposed as the potential target for the anticancer drug discovery. The present study investigated the anticancer effects of the bioactive xanthone garcinone E (GAR E) in mangosteen and explored its underlying mechanism of action. HT-29 and Caco-2 cancer cells were used as in vitro models to study the anticancer effect of GAR E. The findings demonstrated that GAR E inhibited colony formation and wound healing, whereas triggered the production of ROS, which induced mitochondrial dysfunction and apoptosis, causing cell cycle arrest at the Sub G1 phase. Additionally, GAR E treatment elevated the ratio of Bax/Bcl-2 and activated PARP, caspases 3 and 9, and JNK1/2. These GAR E-induced cytotoxic activities and expression of signaling proteins were reversed by the antioxidant N-acetyl-L-cysteine and JNK inhibitor SP600125, indicating the involvement of ROS/JNK signaling pathways. In vivo experiments using an HT-29 xenograft nude mouse model also demonstrated the antitumor effect of GAR E. In conclusion, our findings showed that GAR E might be potentially effective in treating colorectal cancer and provided insights into the development of xanthones as novel chemotherapeutic agents.


Persistent Identifierhttp://hdl.handle.net/10722/329000
ISSN
2023 Impact Factor: 6.9
2023 SCImago Journal Rankings: 1.493
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, Renkai-
dc.contributor.authorZheng, Chengwen-
dc.contributor.authorShiu, Polly Ho Ting-
dc.contributor.authorRangsinth, Panthakarn-
dc.contributor.authorWang, Wen-
dc.contributor.authorKwan, Yiu Wa-
dc.contributor.authorWong, Emily Sze Wan-
dc.contributor.authorZhang, Yanbo-
dc.contributor.authorLi, Jingjing-
dc.contributor.authorLeung, George Pak Heng-
dc.date.accessioned2023-08-05T07:54:31Z-
dc.date.available2023-08-05T07:54:31Z-
dc.date.issued2023-03-29-
dc.identifier.citationBiomedicine and Pharmacotherapy, 2023, v. 162-
dc.identifier.issn0753-3322-
dc.identifier.urihttp://hdl.handle.net/10722/329000-
dc.description.abstract<p>Despite various therapeutic approaches, <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/colorectal-cancer" title="Learn more about colorectal cancer from ScienceDirect's AI-generated Topic Pages">colorectal cancer</a> is among the most fatal <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/disease" title="Learn more about diseases from ScienceDirect's AI-generated Topic Pages">diseases</a> globally. Hence, developing novel and more effective methods for colorectal cancer <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/therapeutic-procedure" title="Learn more about treatment from ScienceDirect's AI-generated Topic Pages">treatment</a> is essential. Recently, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/reactive-oxygen-species" title="Learn more about reactive oxygen species from ScienceDirect's AI-generated Topic Pages">reactive oxygen species</a> (ROS)/JNK <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/signal-transduction" title="Learn more about signaling pathway from ScienceDirect's AI-generated Topic Pages">signaling pathway</a> has been proposed as the potential target for the <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/anticarcinogen" title="Learn more about anticancer drug from ScienceDirect's AI-generated Topic Pages">anticancer drug</a> discovery. The present study investigated the anticancer effects of the bioactive <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/xanthone-derivative" title="Learn more about xanthone from ScienceDirect's AI-generated Topic Pages">xanthone</a> garcinone E (GAR E) in mangosteen and explored its underlying mechanism of action. HT-29 and Caco-2 <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/cancer-cell" title="Learn more about cancer cells from ScienceDirect's AI-generated Topic Pages">cancer cells</a> were used as in vitro models to study the anticancer effect of GAR E. The findings demonstrated that GAR E inhibited colony formation and wound healing, whereas triggered the production of ROS, which induced mitochondrial dysfunction and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/programmed-cell-death" title="Learn more about apoptosis from ScienceDirect's AI-generated Topic Pages">apoptosis</a>, causing <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/cell-cycle-arrest" title="Learn more about cell cycle arrest from ScienceDirect's AI-generated Topic Pages">cell cycle arrest</a> at the Sub <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/g1-phase" title="Learn more about G1 phase from ScienceDirect's AI-generated Topic Pages">G1 phase</a>. Additionally, GAR E treatment elevated the ratio of Bax/Bcl-2 and activated PARP, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/caspase-3" title="Learn more about caspases 3 from ScienceDirect's AI-generated Topic Pages">caspases 3</a> and 9, and JNK1/2. These GAR E-induced cytotoxic activities and expression of signaling proteins were reversed by the antioxidant N-acetyl-L-cysteine and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/phosphotransferase-inhibitor" title="Learn more about JNK inhibitor from ScienceDirect's AI-generated Topic Pages">JNK inhibitor</a> <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/anthra1-9-cdpyrazol-6-2h-one" title="Learn more about SP600125 from ScienceDirect's AI-generated Topic Pages">SP600125</a>, indicating the involvement of ROS/JNK signaling pathways. <em>In vivo</em> experiments using an HT-29 <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/xenograft" title="Learn more about xenograft from ScienceDirect's AI-generated Topic Pages">xenograft</a> <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/nude-mouse" title="Learn more about nude mouse from ScienceDirect's AI-generated Topic Pages">nude mouse</a> model also demonstrated the antitumor effect of GAR E. In conclusion, our findings showed that GAR E might be potentially effective in treating colorectal cancer and provided insights into the development of xanthones as novel chemotherapeutic agents.</p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofBiomedicine and Pharmacotherapy-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectApoptosis-
dc.subjectColorectal cancer-
dc.subjectReactive oxygen species-
dc.subjectXanthone-
dc.titleGarcinone E triggers apoptosis and cell cycle arrest in human colorectal cancer cells by mediating a reactive oxygen species–dependent JNK signaling pathway-
dc.typeArticle-
dc.identifier.doi10.1016/j.biopha.2023.114617-
dc.identifier.scopuseid_2-s2.0-85151273704-
dc.identifier.volume162-
dc.identifier.isiWOS:000966419400001-
dc.identifier.issnl0753-3322-

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