Abstract
Simple SummaryOral 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 G2/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.
Highlights
Among head and neck cancers, oral cancer results in higher morbidity than other head and neck cancers [1]
To investigate the anticancer activity of chrysosplenol D, we first analyzed the viability of Oral squamous cell carcinoma (OSCC) cell lines treated with chrysosplenol D by using the MTT and colony formation assays
We observed that the HSC-3-M3 cell line, a highly metastatic cell line derived from the HSC-3 cell line, exhibited similar sensitivity to chrysosplenol D-induced cell toxicity as did the HSC-3 cell line
Summary
Among head and neck cancers, oral cancer results in higher morbidity than other head and neck cancers [1]. The incidence of oral cancer is high in Melanesia and South-Central Asia owing to the habit of betel nut chewing in these areas [3]. The incidence of oral cancer increased with age and was higher in men than in women in most regions [4]. The survival rate of patients with OSCC has been improving year by year, their prognosis is relatively poor with a high recurrence rate [7]. With the increasing incidence rates of all cancers, 28.4 million new cancer cases are predicted to occur in 2040, indicating a 47% increase in the number of cancer cases from
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