Yang Wang, Yan-Yan Chen, Gui-Bin Gao, Yang-Han Zheng, Nan-Nan Yu, Lan Ouyang, Xuejuan Gao, Nan Li, Shi-Yuan Wen, Shangjia Huang, Qian Zhao, Langxia Liu, Mingrong Cao, Shuixing Zhang, Jing Zhang, Qing-Yu He
Hypertrophic lysosomes are critical for tumor progression and drug resistance; however, effective and specific lysosome targeting compounds for cancer therapy are lacking. Here we conducted a lysosomotropic pharmacophore-based in silico screen in a natural product library (2212 compounds), and identified Polyphyllin D (PD) as a novel lysosome-targeted compound. PD treatment was found to cause lysosomal damage, as evidenced by the blockade of autophagic flux, loss of lysophagy, and the release of lysosomal contents, thus exhibiting anticancer effects on hepatocellular carcinoma (HCC) cell both in vitro and in vivo...
May 21, 2023: Molecular Therapy