Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/ijms24119575
Keywords
natural product; superstolide; glycomics; transcriptomics; phenotypic analysis; 3D spheroid
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ZJ-101, a simplified analog of superstolide A, exhibits potent antiproliferative and antiadhesive effects, making it a potential therapeutic agent. Transcriptomics analysis revealed a unique dysregulation of the endomembrane system by ZJ-101, including selective inhibition of O-glycosylation. In a triple-negative breast cancer spheroid model, ZJ-101 showed potential for reversing 3D-induced chemoresistance, indicating its synergistic therapeutic potential.
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 Neosiphonia Superstes. 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.
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