Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101
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&l...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9575 |
| _version_ | 1797597386042769408 |
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| author | Phillip R. Sanchez Sarah A. Head Shan Qian Haibo Qiu Avishek Roy Zhendong Jin Wei Zheng Jun O. Liu |
| author_facet | Phillip R. Sanchez Sarah A. Head Shan Qian Haibo Qiu Avishek Roy Zhendong Jin Wei Zheng Jun O. Liu |
| author_sort | Phillip R. Sanchez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T03:04:28Z |
| format | Article |
| id | doaj.art-3b8c732b4b4e4098a1bacd51b287779d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:04:28Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3b8c732b4b4e4098a1bacd51b287779d2023-11-18T08:00:59ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411957510.3390/ijms24119575Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101Phillip R. Sanchez0Sarah A. Head1Shan Qian2Haibo Qiu3Avishek Roy4Zhendong Jin5Wei Zheng6Jun O. Liu7National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD 20892, USADepartment of Pharmacology & Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USADepartment of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USADepartment of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USADepartment of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USADepartment of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, IA 52242, USANational Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD 20892, USADepartment of Pharmacology & Molecular Sciences, Johns Hopkins School of Medicine, Baltimore, MD 21205, USAMarine 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.https://www.mdpi.com/1422-0067/24/11/9575natural productsuperstolideglycomicstranscriptomicsphenotypic analysis3D spheroid |
| spellingShingle | Phillip R. Sanchez Sarah A. Head Shan Qian Haibo Qiu Avishek Roy Zhendong Jin Wei Zheng Jun O. Liu Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101 International Journal of Molecular Sciences natural product superstolide glycomics transcriptomics phenotypic analysis 3D spheroid |
| title | Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101 |
| title_full | Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101 |
| title_fullStr | Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101 |
| title_full_unstemmed | Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101 |
| title_short | Modulation of the Endomembrane System by the Anticancer Natural Product Superstolide/ZJ-101 |
| title_sort | modulation of the endomembrane system by the anticancer natural product superstolide zj 101 |
| topic | natural product superstolide glycomics transcriptomics phenotypic analysis 3D spheroid |
| url | https://www.mdpi.com/1422-0067/24/11/9575 |
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