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Keywords = superstolide

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16 pages, 6586 KiB  
Article
Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101
by Phillip R. Sanchez, Sarah A. Head, Shan Qian, Haibo Qiu, Avishek Roy, Zhendong Jin, Wei Zheng and Jun O. Liu
Int. J. Mol. Sci. 2023, 24(11), 9575; https://doi.org/10.3390/ijms24119575 - 31 May 2023
Cited by 1 | Viewed by 3452
Abstract
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 [...] Read more.
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. Full article
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