114 / 2021-10-24 11:38:41

Fascaplysin derivative Mar-03 inhibit NSCLC tumor growth by targeting ferroptosis

Mar-03,NSCLC,ferroptosis

Non-small cell lung cancer (NSCLC) is one of the major cancer-related causes of morbidity and mortality worldwide. Natural marine products represent a rich source of bioactive compounds. Fascaplysin is an isolated from the sponge Fascaplysinopsissp. Fascaplysin has anti-tumor effects such as CDK4 specific inhibition, DNA chimerism, and neovascularization inhibition. In order to further improve its anticancer activity, target selectivity as well as in vivo toxicity, we named it Mar-03 based on the synthesis of its brominated derivative with fascaplysin. We found that Mar-03 had the effect of inducing ferroptosis in cancer cells. In cellular experiments, Mar-03 inhibited the growth of cancer cells, and the phenomenon was relieved by Lip-1, an ferroptosis inhibitor. Mar-03 well induced the ferroptosis in cancer cells with depletion of antioxidant defence and ferroprotein. The ferroptosis indicators SLC7A11, GPX4, and FTH1 concentration-dependent were down-regulated by Mar-03 and resulted in an increase in intracellular free ferrous ions, thus cause a rapid lipid ROS generation, and prevented the expansion of cancer cells. In our previous experiments, Mar-03 played a good role in tumor inhibition in tumor-bearing mice and showed the inhibitory effect on tumor tissue growth. These results suggest that Mar-03 has a translational value for anticancer drug targeting ferroptosis.