Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101-Reference-Cited by-同舟云学术

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

Published:2023-05-31 Issue:11 Volume:24 Page:9575
ISSN:1422-0067
Container-title:International Journal of Molecular Sciences
language:en
Short-container-title:IJMS

Author:

Sanchez Phillip R.¹²,Head Sarah A.²^ORCID,Qian Shan³,Qiu Haibo³^ORCID,Roy Avishek³,Jin Zhendong³,Zheng Wei¹^ORCID,Liu Jun O.²

Affiliation:

1. National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD 20892, USA

2. Department of Pharmacology & Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA

3. Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USA

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 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.

Funder

National Center for Advancing Translational Sciences

National Institutes of Health

FAMRI grant

Postdoctoral Intramural Research Training Award

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Link

https://www.mdpi.com/1422-0067/24/11/9575/pdf

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