The Biological Function Of Several Material Through Autophagy Modulation

Autophagy is a dynamic process of subcellular degradation related to lysosomes, which has recently sparked great interest as it is now recognized to be involved in various developmental processes and many diseases including cancer and neurodegeneration. Autophagy can function as a cytoprotective mechanism; however, it also has the capacity to cause cell death. A better understanding of autophagy is needed to allow its manipulation for therapeutic purposes, and new insights into the molecular mechanisms of autophagy are now leading to the discovery of exciting new potential drug targets.Here we present two of our several projects on autophagy, focusing on autophagy induced by nano fullerene derivatives in the first part and a topoisomerase inhibitor Hoechst33342 in the second part. In chapter 2, we showed that the crystal of nano fullerene and its derivatives stably dispersed in water, induced aberrant autophagy with increased autophagosome formation and reduced autophagic turnover in a photo-enhanced and free radical-dependent fashion. The further studies revealed by my teammates that autophagy-inducing dose of nano-C60 did not directly cause cell death but sensitized chemotherapeutic killing of normal and drug-resistant cancer cells with an autophagy-essential gene Atg5.In chapter 3, Hoechst33342 was showed to induce massive autophagy in HeLa c cells. More strikingly, this autophagy serves as a cytoprotective mechanism against HO-induced apoptosis, one of the tumor suppressor mechanisms. Very intriguingly, co-administration of autophagy inhibitory reagents and HO greatly induced cells to apoptosis. In a word, these two novel projects are meaningful investigations toward the aim of developing autophagy-targeting drugs and have significant values.