| 초록 |
Autophagy supports homeostasis by breaking down and recycling damaged or unnecessary proteins and organelles within a cell. In a tumor region of a developed tumor, autophagy is upregulated to help tumor cell survival, suggesting that autophagy inhibition may bring antitumor activity. Herein, we have developed helical polypeptide that act as a downstream autophagy inhibitor. Morpholine group attached in the side chain shows effective lysosome targeting and membrane destabilizing abilities. Once the peptide enters the lysosomal membrane, lysosomal acidification is prevented to block cellular degradation. As the large amounts of non-degraded cytosolic components are accumulated, autophagy process is inhibited. Then, level of reactive oxygen species is increased to disrupt mitochondria initiating apoptotic cell death. Further in vitro studies are performed to confirm that the polypeptide is a safe and promising tool to treat cancer by inhibiting autophagy process. |
