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Title: | Chrysosplenol D Triggers Apoptosis through Heme Oxygenase-1 and Mitogen-Activated Protein Kinase Signaling in Oral Squamous Cell Carcinoma |
Authors: | Hsieh, MJ;Lin, CC;Lo, YS;Chuang, YC;Ho, HY;Chen, MK |
Keywords: | chrysosplenol D;apoptosis;autophagy;heme oxygenase-1;oral squamous cell carcinoma |
Date: | 2021 |
Issue Date: | 2022-08-05T09:43:44Z (UTC)
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Publisher: | MDPI |
Abstract: | Simple Summary Oral squamous cell carcinoma (OSCC) accounts for the most malignancies. A GLO-BOCAN 2020 report estimated 377,713 new cases of oral cancer and 177,757 deaths due to oral cancer in 2020. Chrysosplenol D, a flavonol isolated from Artemisia annua L., can exert an-ticancer effects. This study investigated the anticancer property of chrysosplenol D and its un-derlying mechanism in oral squamous cell carcinoma. We observed that chrysosplenol D reduced cell viability, cell cycle arrest, apoptosis and autophagy in OSCC. Moreover, the upregulation of heme oxygenase-1 (HO-1) was found to be critical for chrysosplenol D-induced apoptotic cell death that patients with head and neck cancer had lower HO-1 expression. The findings of the present study indicated that chrysosplenol D exerts anticancer effects on OSCC by suppressing the MAPK pathway and activating HO-1 expression. Suggest that chrysosplenol D might be a potential anticancer agent for treating OSCC. Chrysosplenol D, a flavonol isolated from Artemisia annua L., can exert anticancer effects. This study investigated the anticancer property of chrysosplenol D and its underlying mechanism in oral squamous cell carcinoma (OSCC). We observed that chrysosplenol D reduced cell viability and caused cell cycle arrest in the G(2)/M phase. The findings of annexin V/propidium iodide staining, chromatin condensation, and apoptotic-related protein expression revealed that chrysosplenol D regulated apoptosis in OSCC. Furthermore, chrysosplenol D altered the expression of the autophagy marker LC3 and other autophagy-related proteins. Phosphatidylinositol 3-kinase/protein kinase B, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase (MAPK) were downregulated by chrysosplenol D, and the inhibition of these pathways significantly enhanced chrysosplenol D-induced cleaved poly (ADP-ribose) polymerase activation. Moreover, the upregulation of heme oxygenase-1 (HO-1) was found to be critical for chrysosplenol D-induced apoptotic cell death. The analysis of clinical data from The Cancer Genome Atlas and Gene Expression Omnibus datasets revealed that patients with head and neck cancer had lower HO-1 expression than did those with no head and neck cancer. The findings of the present study indicated that chrysosplenol D exerts anticancer effects on OSCC by suppressing the MAPK pathway and activating HO-1 expression. |
URI: | http://dx.doi.org/10.3390/cancers13174327 https://www.webofscience.com/wos/woscc/full-record/WOS:000695559400001 https://ir.csmu.edu.tw:8080/handle/310902500/23841 |
Relation: | CANCERS ,2021,v13,issue 17 |
Appears in Collections: | [中山醫學大學研究成果] 期刊論文
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