calothrixin-a and Lung-Neoplasms

CAA45 is a calothrixin A (CAA) analogue with anti-cancer activity at nanomolar concentration. This study aimed to investigate the anti-lung cancer activity of CAA45 and explore its mechanisms of actions.. CAA and CAA45 were synthesized and their inhibition on DNA topoisomerase I (Topo I) performed by evaluating the relaxation of supercoiled pBR322 plasmid DNA and their anti-lung cancer capacity determined by cytotoxic assays, cell migration, cell cycle, cell apoptosis, cell autophagy and related signaling proteins expression by western blot.. CAA45 exerted its anti-lung cancer effect via inhibition of Topo I, resulting in cell cycle arrest and cell migration, induction of mitochondria mediated cell apoptosis and autophagy via PI3K/Akt/JNK/p53 pathway. All these observations suggested that CAA45 could be a promising lead for anti-cancer drug discovery.

Topics: A549 Cells; Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Cycle; Cell Line, Tumor; Cell Movement; Humans; Indole Alkaloids; Lung Neoplasms; Male; Mice, Inbred BALB C; Neoplasm Transplantation; Topoisomerase I Inhibitors