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

Phillip Sanchez; Sarah Head; Shan Qian; Haibo Qiu; Avishek Roy; Zhendong Jin; Wei Zheng; Jun Liu

doi:10.3390/ijms24119575

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

Journal article

Open access

Peer reviewed

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

Phillip Sanchez, Sarah Head, Shan Qian, Haibo Qiu, Avishek Roy, Zhendong Jin, Wei Zheng and Jun Liu

International journal of molecular sciences, Vol.24(11), 9575

06/01/2023

DOI: 10.3390/ijms24119575

PMCID: PMC10253484

PMID: 37298526

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https://doi.org/10.3390/ijms24119575View

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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.

Cell Cycle

Morphology

Natural Products

Pharmacology

Cancer

Cell adhesion & migration

Chemoresistance

Cytotoxicity

Drug dosages

Endoplasmic reticulum

Glycosylation

Lectins

Spheroids

Transcriptomics

Tumor cell lines

Details

Title: Subtitle: Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101
Creators: Phillip Sanchez - National Center for Advancing Translational Sciences
Sarah Head - Johns Hopkins Medicine
Shan Qian - University of Iowa
Haibo Qiu - University of Iowa
Avishek Roy - University of Iowa
Zhendong Jin - University of Iowa
Wei Zheng - National Center for Advancing Translational Sciences
Jun Liu - Johns Hopkins Medicine
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.24(11), 9575
DOI: 10.3390/ijms24119575
PMID: 37298526
PMCID: PMC10253484
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Publisher: MDPI AG
Grant note: name: National Center for Advancing Translational Sciences; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1R21CA204836-01, 5T32GM008763; name: FAMRI grant; name: Postdoctoral Intramural Research Training Award
Language: English
Date published: 06/01/2023
Academic Unit: Pharmaceutical Sciences and Experimental Therapeutics; Medicinal and Natural Products Chemistry
Record Identifier: 9984426855102771

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