Cell Death Induced by the Combination of Ephedra sinica Extract and Radiation in HNSCC is Positively Related to BAX and p-MLKL Expression.

BACKGROUND: Numerous studies have proven the efficacy and safety of natural products, and are widely used as attractive cancer treatments. The investigation of effective natural products for improving cancer treatment is a promising strategy. Combination treatment with radiosensitizers and radiotherapy (RT) is considered necessary for therapeutic improvement in head and neck squamous cell carcinoma(HNSCC). OBJECTIVE: This study aims to investigate whether Ephedra sinica (ES) extract could induce selective cell death in cancer cells and serve as a radiosensitizer for HNSCC. METHODS: HNSCC cells were pretreated with ES extract before radiation, and the radiosensitizing activity was assessed using a colony formation assay. Radiation-induced cell death was evaluated using an annexinV-FITC assay. Western blotting was performed to confirm cell death-related gene expression, including apoptosis and necrosis markers. RESULTS: ES extract significantly inhibited HNSCC cell viability (FaDu and SNU1076), while having minimal effect on normal HaCaT cells. When HNSCC cells were irradiated with 2, 4, or 8 Gy and cultured with ES extract (25 µg/mL), they exhibited increased radiation sensitivity compared to non-treated cells. The combination of ES extract and radiation resulted in increased cell death compared to non-treated, ES-treated, or irradiated cells. The apoptosis marker BAX and necrosis marker p-MLKL expression levels were also elevated following the combination treatment. CONCLUSION: ES extract demonstrated significant cytotoxic potential in HNSCC cells without affecting normal cells. It enhanced the radiosensitivity of HNSCC cells by upregulating BAX and p-MLKL expression, leading to increased cell death. These results suggest ES extract exhibits a potential radiosensitizing capacity in HNSCC.

Risk of cancer in patients with recurrent aphthous stomatitis in Korea: A nationwide population-based study.

ABSTRACT: The relationship between recurrent aphthous stomatitis (RAS), a common mucosal lesion, and cancer has not been demonstrated. This study investigated the risk for developing cancer in patients with RAS, based on data from Korea's National Health Insurance Sharing Service (NHISS). Nationwide population-based cohort data from 2005 to 2009 provided by the NHISS was used. The group diagnosed with RAS for 5 years and an undiagnosed control group were constructed through 1:1 propensity score matching (PSM). The experimental design compared the incidence rate of a cancer diagnosis from 2010 to 2015 between these 2 groups. After identifying 13,808 people that met our inclusion criterion from a 1 million cohort group, 13,808 controls were included in the study through PSM. Among all cancers, pancreatic cancer had an adjusted hazard ratio of 1.26 (95% confidence interval: 1.01-1.57, P < .041). For the rest of the cancers, there was no significant incidence rate. RAS was associated with an increased risk of pancreatic cancer in the analysis using large population-based cohort data. Further long-term follow-up studies are needed.

Silence of Hippo Pathway Associates with Pro-Tumoral Immunosuppression: Potential Therapeutic Target of Glioblastomas.

The critical role of the Hippo pathway has been recently investigated in various cancers, but little is known about its role in glioblastoma (GBM). In order to evaluate the clinical relevance of the Hippo pathway in GBM, we generated a core gene expression signature from four different previously-established silence of Hippo pathway (SOH) signatures. Based on a newly generated core SOH signature, a SOH and active Hippo pathway (AH) was predicted in GBM samples from The Cancer Genome Atlas (TCGA) and validated in a separate cohort. A comparative analysis was performed on multi-panel genomic datasets from TCGA and the possible association of SOH with immune activity and epithelial mesenchymal transition was also evaluated. The SOH signature was associated with poor prognosis in GBM in both cohorts. Expression levels of CTGF and CYR61, the most reliable and well-known downstream targets of YAP1, were markedly increased in the SOH subgroup of GBM patients. SOH signature was strongly associated with a high immune signature score and mesenchymal features. Genes differentially expressed between SOH and AH groups revealed many markers for inhibitory immune checkpoints and M2-polarized macrophages were upregulated in the SOH subgroup, suggesting that SOH may induce the resistance of cancer cells to host immune response in GBM. In summary, SOH is significantly associated with the poor prognosis of GBM patients and is possibly mediated by pro-tumoral immunosuppression.

Moscatilin Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma Cells via JNK Signaling Pathway.

Dendrobii Herba is an herbal medicine that uses the stems of Dendrobium species (Orchidacea). It has been traditionally used to treat fever, hydrodipsomania, stomach disorders, and amyotrophia. In our previous study, a bibenzyl compound, moscatilin, which is isolated from Dendrobii Herba, showed potent cytotoxicity against a FaDu human pharyngeal squamous carcinoma cell line. Prompted by this finding, we performed additional studies in FaDu cells to investigate the mechanism of action. Moscatilin induced FaDu cell death by using 5 µM of concentration and by mediating apoptosis, whereas cell proliferation following treatment with 1 µM of moscatilin was not suppressed to the same levels as by the anti-cancer agent, cisplatin. Apoptosis-related protein expression (cleaved caspase-8, cleaved caspase-7, cytochrome c, cleaved caspase-9, cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP) was increased by treating with 5 µM of moscatilin. This suggests that moscatilin-mediated apoptosis is associated with the extrinsic and intrinsic apoptotic signaling pathways. In addition, moscatilin-induced apoptosis was mediated by the c-Jun N-terminal kinase (JNK) signaling pathway. Overall, this study identified additional biological activity of moscatilin derived from natural products and suggested its potential application as a chemotherapeutic agent for the management of head and neck squamous cell carcinoma.

Pretreatment with a grape seed proanthocyanidin extract downregulates proinflammatory cytokine expression in airway epithelial cells infected with respiratory syncytial virus.

Respiratory syncytial virus (RSV) infections are associated with significant morbidity and mortality. Inflammation is mediated by cytokine secretion from RSV­infected airway epithelial cells. Grape seed proanthocyanidin extract (GSPE) exhibits potent antioxidant capacity, as well as anti­bacterial, anti­viral, anti­carcinogenic, anti­inflammatory and anti­allergic actions. However, few studies have explored the anti­inflammatory effects of GSPE on airway epithelial cells infected with RSV. Airway epithelial A549 cells were pretreated with GSPE and its effects on cytokine production during RSV infection were investigated. A549 cells were infected with RSV, with or without GSPE pretreatment, and cultured for 24, 48 and 72 h. The expression of interleukin (IL)­1ß, IL­6 and IL­8, were measured by reverse transcription­quantitative polymerase chain reaction, ELISA and western blotting. RSV infection induced significant increases in proinflammatory cytokine expression. However, GSPE pretreatment decreased the mRNA and protein expression levels of IL­1ß, IL­6 and IL­8. GSPE regulated the immune response by reducing the RSV­induced transcription of proinflammatory cytokines in airway epithelial cells, suggesting that GSPE helps to prevent RSV­induced airway disease.