ABSTRACT
Lung cancer is the leading type of cancer worldwide today. Kinases play a crucial role in mediating the signaling pathways, and it directs to control several necessary cellular processes. Conversely, the deregulation of tyrosine kinases leads to oncogenic conversion, uncontrolled cell proliferation and tumorigenesis. Tyrosine kinases are largely deregulated in lung cancer and specifically in non-small cell lung cancer (NSCLC). Therefore, the inhibition of pathogenic kinases is a breakthrough development in cancer research, treatment and care, which clinically improve the quality of life. In the last decades, various single or combination inhibitors are approved by U.S Food and Drug Administration (FDA) and commercially available in clinics, and currently, several preclinical studies are ongoing and examining the kinase inhibitors. However, many gaps remain in understanding the mechanisms of kinase inhibitors and their selectivity. In this analysis, we focus on a class of receptor and non-receptor tyrosine kinase inhibitors and their novel role in lung cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Protein Kinase Inhibitors/pharmacology , Protein-Tyrosine Kinases , Receptor Protein-Tyrosine Kinases , Antineoplastic Agents/pharmacology , Carcinogenesis/drug effects , Carcinogenesis/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Drug Development , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/metabolism , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/metabolism , Signal Transduction/drug effectsABSTRACT
The sulfated polysaccharide (SP) was isolated from the brown alga S. tenerrimum. The chemical composition of SP composed of 57 ± 0.29% of total sugar, 1.14 ± 0.28% of protein and 25.6 ± 0.45% of sulfate. Elemental analysis of SP shows 28.8% of carbon, 4.02% of hydrogen and 0.29% of nitrogen. The molecular weight of SP was estimated as 31 kDa. Further, the SP was characterized through FT-IR, 1H-NMR, GC-MS, XRD and TGA analysis. The DPPH and ABTS radical scavenging activity of SP showed 34.03-62.70% and 22.94-38.04% at the concentration of 25-125 µg/mL respectively. In addition, SP exerted a protective role against H2O2 mediated oxidative stress in fibroblast cells through scavenging intracellular ROS. Furthermore, ROS generation and cell death were significantly decreased in SP treated zebrafish embryos at 150 µg/mL, whereas the survival rate was increased. The protective effect of SP against oxidative stress might be utilized in pharmacological industries.
