Ultraviolet radiation is a major environmental harmful factor on human skin. In this paper, we investigate the potential mechanism of Houttuynia cordata extract on UVB-induced HaCaT keratinocyte cell death and inflammation. We found that Houttuynia cordata ethyl acetate extract fraction (HC-EA) protected against UVB-induced cell damage. The HPLC results indicate that quercitrin and hyperoside are the major polyphenolics in HC-EA and are responsible for providing protection against UVB-induced cell death. These responses were associated with the regulation of caspase-9 and caspase-3 activation, which rescued HaCaT cells from UVB-induced apoptosis. In addition, HC-EA, quercitrin, and hyperoside attenuated UVB-induced inflammatory mediators, including IL-6, IL-8, COX-2, and iNOS. Furthermore, the treatment of cells with HC-EA and its active compounds abolished intracellular ROS and increased levels of heme oxygenase-1 and superoxide dismutase. UVB-induced ROS production mediated Akt and mitogen activated protein kinases (MAPKs) pathways, including p38, ERK, and JNK. Our results show HC-EA, quercitrin, and hyperoside decreased UVB-induced p38 and JNK phosphorylation, while increasing ERK and Akt phosphorylation. MAPKs and Akt mediated cell survival and death were confirmed by specific inhibitors to Akt and MAPKs. Thus, HC-EA, which contains quercitrin and hyperoside, protected keratinocyte from UVB-induced oxidative damage and inflammation through the modulation of MAPKs and Akt signaling.

Cervical cancer is a leading cause of gynecological malignancies and cancer-related deaths among women worldwide. This study investigates the anti-cancer activity of Thua Nao, a Thai fermented soybean, against HeLa cervical carcinoma cells, and explores its underlying mechanisms. Our findings reveal that the ethyl acetate fraction of Thua Nao (TN-EA) exhibits strong anti-cancer potential against HeLa cells. High-performance liquid chromatography (HPLC) analysis identified genistein and daidzein as the major isoflavones in TN-EA responsible for its anti-cancer activity. TN-EA and genistein reduced cell proliferation and induced G2/M phase arrest, while daidzein induced G1 arrest. These responses were associated with the downregulation of cell cycle regulators, including Cyclin B1, cycle 25C (Cdc25C), and phosphorylated cyclin-dependent kinase 1 (CDK-1), and the upregulation of the cell cycle inhibitor p21. Moreover, TN-EA and its active isoflavones promoted apoptosis in HeLa cells through the intrinsic pathway, evidenced by increased levels of cleaved Poly (ADP-ribose) polymerase (PARP) and caspase-3, loss of mitochondrial membrane potential, and the downregulation of anti-apoptotic proteins B-cell leukemia/lymphoma 2 (Bcl-2), B-cell lymphoma-extra-large (Bcl-xL), cellular inhibitor of apoptosis proteins 1 (cIAP), and survivin. Additionally, TN-EA and its active isoflavones effectively reduced cell invasion and migration by downregulating extracellular matrix degradation enzymes, including Membrane type 1-matrix metalloproteinase (MT1-MMP), urokinase-type plasminogen activator (uPA), and urokinase-type plasminogen activator receptor (uPAR), and reduced the levels of the mesenchymal marker N-cadherin. At the molecular level, TN-EA suppressed STAT3 activation via the regulation of JNK and Erk1/2 signaling pathways, leading to reduced proliferation and invasion of HeLa cells.

Gastric cancer has one of the highest incidence rates of cancer worldwide while also contributing to increased drug resistance among patients in clinical practice. Herein, we have investigated the role of diclofenac (DCF) on sensitizing cisplatin resistance in signet ring cell gastric carcinoma cells (SRCGC). Non-toxic concentrations of DCF significantly augmented cisplatin-induced cell death in cisplatin-resistant SRCGC cells (KATO/DDP) but not in cisplatin-sensitive SRCGC cells (KATOIII). Consistently, concomitant treatment of DCF and cisplatin significantly enhanced autophagic cell death due to overproduction of intracellular reactive oxygen species (ROS). At the molecular level, the induction of ROS has been associated with a reduction in antioxidant enzymes expression while inhibiting nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Moreover, the combination of DCF and cisplatin also inhibited the expression of survival proteins including Bcl-2, Bcl-xL, cIAP1 and cyclin D1 in KATO/DDP cells when compared with cisplatin alone. This was due, at least in part, to reduce MAPKs, Akt, NF-κB, AP-1 and STAT-3 activation. Taken together, our results suggested that DCF potentiated the anticancer effect of cisplatin in SRCGC via the regeneration of intracellular ROS, which in turn promoted cell death as an autophagy mechanism and potentially modulated the cell survival signal transduction pathway.

High-grade osteosarcoma (HGOS) is the most common primary malignant bone tumor in children and adolescents. Poor response to chemotherapy is linked to worse prognosis and increased risk of recurrence and metastasis. However, current assessment methods, such as tumor necrosis evaluation, are time-consuming and delay treatment decisions. Thus, identifying molecular pathways and predictive biomarkers is essential for guiding early therapeutic strategies. In this study, RNA-seq analysis of HGOS tissues revealed enrichment of cholesterol biosynthesis and mitotic pathways in poor responders. Additionally, high HMGCR expression, as analyzed from TCGA data, was associated with poor prognosis in sarcoma. Functional validation using SaOS-2 cells, which exhibited poor drug sensitivity and elevated HMGCR levels, demonstrated that simvastatin enhanced the efficacy of cisplatin and doxorubicin by inducing mitochondrial-mediated apoptosis and downregulating anti-apoptotic proteins. Simvastatin also reduced cell migration and invasion by suppressing epithelial–mesenchymal transition and extracellular matrix degradation. Mechanistically, simvastatin disrupted Ras prenylation and inhibited downstream oncogenic signaling pathways, including Akt/mTOR and Akt/GSK3, which regulate survival and metastasis-associated gene expression. These findings suggest that the cholesterol biosynthesis pathway particularly plays a critical role in chemoresistance and metastasis in HGOS and may serve as a promising predictive molecular target for guiding early therapeutic strategies.

Background/Objectives: Gastric cancer (GC) remains a major burden in Northern Thailand. Elevated interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A) expression are linked with poor prognosis and tumor progression in gastric cancer. However, the concordance of VEGF-A and IL-8 gene expression profiles and their association with chemotherapy and survival outcomes remain unclear. This study aims to characterize VEGF-A and IL-8 gene expression profiles to address these knowledge gaps. Methods: We analyzed mRNA expression of VEGF-A and IL-8 in 83 gastric mucosal tissue samples from advanced GC patients using RT-qPCR. Expression profiles were reported in distribution format, Kaplan–Meier survival curves, and multivariable Cox models to identify independent prognostic factors. Pre- and post-treatment expression patterns were observed. Results: IL-8 overexpression was found in 83.33% of patients, while VEGF-A overexpression was found in 44.23%. Baseline IL-8 and VEGF-A expression levels were not significantly associated with overall survival. However, paired sample analysis showed post-chemotherapy suppression of IL-8 and VEGF-A expression, with a small percentage of downregulation in a subgroup of patients 33.3% and 30%, respectively. Conclusions: VEGF-A and IL-8 display concordant distribution of expression patterns but differ in downregulation by the same chemotherapy regimen. Although baseline expression lacked independent prognostic value, non-frequent downregulation of VEGF-A and IL-8 occurred post-chemotherapy in Thai advanced gastric cancer patients, suggesting its potential to be a biomarker for chemoresistance. These findings support personalized molecular profiling of VEGF-A expression to identify candidates who may get the benefit from early VEGF-targeted therapies in Thai GC patients.

Background/Objectives: Gastric cancer (GC) remains a major health burden in Northern Thailand. Elevated expression of interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A) is often associated with poor prognosis and tumor progression in gastric cancer. However, the concurrent expression of VEGF-A and IL-8 regarding chemotherapy response and survival outcomes in Thai patients remains poorly understood. This study characterizes VEGF-A and IL-8 expression profiles in Northern Thai gastric cancer patients to fill these knowledge gaps. Methods: mRNA expression of VEGF-A and IL-8 was analyzed in 83 advanced GC patients using RT-qPCR. Outcomes were evaluated by using Kaplan-Meier curves and multivariable Cox proportional-hazard models to identify independent prognostic factors. Results: VEGF-A was upregulated in 31.51% of patients, while IL-8 was elevated in 71.15%. No significant correlation was found between VEGF-A and IL-8; 53.19% of cases showed discordant patterns (high IL-8 level with low VEGF-A level). Post-treatment VEGF-A induction was observed in a subset of patients. Multivariable analysis identified VEGF-A overexpression as an independent predictor of poor prognosis (Hazard Ratio: 2.09; P<0.05). Neoadjuvant chemotherapy was associated with superior survival compared to adjuvant regimens. Conclusions: VEGF-A and IL-8 display unique expression patterns and differential responses to chemotherapy. The independent prognostic value of VEGF-A and its compensatory upregulation highlight its potential as a clinically actionable biomarker. These findings support personalized molecular profiling to guide anti-angiogenic and combinatorial therapies in Northern Thai GC patients.