Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101

oleh: Phillip R. Sanchez, Sarah A. Head, Shan Qian, Haibo Qiu, Avishek Roy, Zhendong Jin, Wei Zheng, Jun O. Liu

Format: Article
Diterbitkan: MDPI AG 2023-05-01

Deskripsi

Marine natural products represent a unique source for clinically relevant drugs due to their vast molecular and mechanistic diversity. ZJ-101 is a structurally simplified analog of the marine natural product superstolide A, isolated from the New Caledonian sea sponge <i>Neosiphonia Superstes</i>. The mechanistic activity of the superstolides has until recently remained a mystery. Here, we have identified potent antiproliferative and antiadhesive effects of ZJ-101 on cancer cell lines. Furthermore, through dose–response transcriptomics, we found unique dysregulation of the endomembrane system by ZJ-101 including a selective inhibition of O-glycosylation via lectin and glycomics analysis. We applied this mechanism to a triple-negative breast cancer spheroid model and identified a potential for the reversal of 3D-induced chemoresistance, suggesting a potential for ZJ-101 as a synergistic therapeutic agent.