Waixenicin A, a bioactive extract of soft coral Sarcothelia edmondsoni, has been shown to be anti-neoplastic. However, its mechanisms of action remain unclear. Cancer stem cells (CSCs) and associated stemness factors are implicated in lung cancer. Here, we investigated the role of Waixenicin A on CSCs-like and metastatic lung cancer cells. We demonstrated and compared TRPM7 expression in the non-tumor lung tissues or bronchial epithelial 16-HBE cell line. TRPM7 was aberrantly expressed in the cancer tissues and SPCA-1, NCI-H520, SK-MES-1, A549 and 95D cell lines. Increased TRPM7 expression was associated with enhanced SOX2, KLF4, and CD133, Hsp90α, uPA, and MMP2 expression in lung cancer cells. TRPM7-silencing inhibited epithelial-to-mesenchymal transition (EMT), suppressed stemness markers and phenotypes, concomitantly suppressed Hsp90α/uPA/MMP2 axis. Coincidently, Waixenicin A treatment downregulated TRPM7 and oncogenic markers; Waixenicin A also attenuated the ability of lung cancer cells to form tumorspheres, in vitro. In validation, our clinicopathological analyses showed that a higher TRPM7 expression was positively correlated with the larger tumor size (p = 0.007), positive lymph node metastasis (p = 0.005) and disease grade (p = 0.003). Through its ability to inhibit Hsp90α/uPA/MMP2 signaling and suppress TRPM7 expression, we showed that Waixenicin A is a potential anticancer therapeutic agent for treating malignant lung cancer.

Background: The main aim of this research was to explore the role and mechanism of Andrographolide (Andro) in controlling non-small cell lung cancer (NSCLC) cell proliferation. Methods: Human NSCLC H1975 cells were treated with Andro (0–20 µM) for 4–72 h. B-cell leukemia/lymphoma 2 (Bcl-2)-antagonist/killer (Bak)-small interfering RNA (siRNA) (Bak-siRNA) and fructose-1,6-bisphosphatase (FBP1)-siRNA were transfected into H1975 cells to inhibit the endogenic Bak and FBP1 expression, respectively, and their expressions were detected by real-time quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and western blotting (WB). Cellular proliferation ability was determined through various assessments, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and cell counting kit-8 (CCK-8) assays. Cell apoptosis ability was measured using flow cytometry. Pro-apoptotic-related proteins (cleaved caspase 9, cleaved caspase 8, and cleaved caspase 3) and mitochondrial apoptosis pathway proteins [Bcl2-associated X (Bax), Bak, Bcl-2, and cytochrome C (cyto C)] were assessed by WB. Aerobic glycolysis-associated genes [pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), and glucose transporter 1 (GLUT1)] and gluconeogenesis genes [phosphoenolpyruvate carboxykinase 1 (PEPCK1), fructose-1,6-bisphosphatase 1 (FBP1), and phosphofructokinase (PFK)] were measured by qRT-PCR. The mitochondrial membrane depolarization sensor, 5, 50, 6, 60-tetrachloro-1, 10, 3, 30 tetraethyl benzimidazolo carbocyanine iodide (JC-1) assay was used for the measurement of mitochondrial membrane potential (ΔΨm). Additionally, glycolytic metabolism, lactate production, and adenosine triphosphate (ATP) synthesis were also analyzed. Results: Andro inhibited human NSCLC cellular proliferation and induced apoptosis in a dose-time or dose-dependent manner via activation of the mitochondrial apoptosis pathway. Andro inhibited glycolysis, promoted the gluconeogenesis pathway, and increased the levels of cleaved caspase 9, cleaved caspase 8, cleaved caspase 3, Bax, Bak, PEPCK1, FBP1, and PFK, and decreased the levels of Bcl-2, PKM2, LDHA, and GLUT1. Moreover, it also decreased the ΔΨm and facilitated the release of cyto C from mitochondria into the cytoplasm. Furthermore, Andro enhanced the mitochondrial translocation of Bak, glucose uptake, lactate release, and intracellular ATP synthesis. Suppression of endogenic Bak and FBP1 expression significantly reduced the effects of Andro in H1975 cells. Conclusions: Andro represses NSCLC cell proliferation through the activation of the mitochondrial apoptosis pathway and by reprogramming glucose metabolism.

Background: Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer. Methods: Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples. Results: Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p<0.05). A cancer-related microbiota model was constructed and produced an area under the curve of 0.74 in the training set, indicating discrimination between subjects with and without cancer. Conclusions: Characterization of microbiota in saliva, CT and PT from Chinese lung cancer patients revealed little difference between CT and PT, indicating that the tumor and its microenvironment might influence the local microbiome. A model to distinguish between CT and PT was constructed, which has the potential to enhance our comprehension of the involvement of microbiota in the pathogenesis of lung cancer and identify novel therapeutic targets.

Aim: A meta-analysis was conducted to assess the application of circulating cell-free DNA (cfDNA) in non-small-cell lung carcinoma (NSCLC) screening, EGFR and KRAS mutation detection. Materials & m...