Lung cancer is the leading type of malignancy in terms of occurrence and mortality in the global context. STAT3 is an oncogenic transcription factor that is persistently activated in many types of human malignancies, including lung cancer. In the present report, new oxadiazole conjugated indazoles were synthesized and examined for their anticancer potential in a panel of cancer cell lines. Among the new compounds, 2-(3-(6-chloro-5-methylpyridin-3-yl)phenyl)-5-(1-methyl-1H-indazol-3-yl)-1,3,4-oxadiazole (CHK9) showed consistently good cytotoxicity towards lung cancer cells with IC50 values ranging between 4.8–5.1 µM. The proapoptotic effect of CHK9 was further demonstrated by Annexin-FITC staining and TUNEL assay. In addition, the effect of CHK9 on the activation of STAT3 in lung cancer cells was examined. CHK9 reduced the phosphorylation of STAT3Y705 in a dose-dependent manner. CHK9 had no effect on the activation and expression of JAK2 and STAT5. It also reduced the STAT3-dependent luciferase reporter gene expression. CHK9 increased the expression of proapoptotic (p53 and Bax) proteins and decreased the expression of the antiapoptotic (Bcl-2, Bcl-xL, BID, and ICAM-1) proteins. CHK9 displayed a significant reduction in the number of tumor nodules in the in vivo lung cancer model with suppression of STAT3 activation in tumor tissues. CHK9 did not show substantial toxicity in the normal murine model. Overall, CHK9 inhibits the growth of lung cancer cells and tumors by interfering with the STAT3 signaling pathway.
Silk, a natural biopolymer, is used for both textile and biomedical applications. Natural biopolymers are currently being used in various fields such as tissue engineering, wound healing, and food packaging based on their intrinsic qualities of safety, biocompatibility, and biodegradability, which make them the material of choice. Silk fibroin proteins from the Antheraea mylitta wild silkworm are the least studied in the field of biomaterials. The β-sheet structures found in non-mulberry silk fibroin protein improve its mechanical properties. The present study was undertaken to regenerate water-soluble A. mylitta silk fibroin to improve its applications and enhance fabrication efficiency. The silk fibroin was regenerated by dissolving degummed silk fibers in calcium nitrate tetrahydrate salt at 100°C for 3 h. The biophysical characterization of regenerated silk fibroin was carried out by X-ray diffraction, scanning electron microscope, Therapeutic Goods Administration, Fourier-transform infrared spectroscopy, and differential scanning calorimetry, confirming the indigenous aspects of the "regenerated silk fibroin (RSF)". CD spectra were employed to track α-helix to β-sheet conformational transition changes in RSF. MTT assays using NIH3T3 fibroblast cells revealed that the RSF exhibited no toxicity and resulted in the proliferation of cells.
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