The correlation between cellular O-GlcNAcylation and sensitivity to O-GlcNAc inhibitor in colorectal cancer cells

Sep 21, 2026

O-GlcNAc signaling upregulation is linked to the development and progression of many malignancies, including colorectal cancer. This study examined eight colorectal cancer cell lines and one non-cancerous line for OGT, OGA, and total protein O-GlcNAcylation profiles, then assessed sensitivity to OSMI-1 (Os), an OGT inhibitor. Os suppressed viability of all tested colorectal cancer lines in a dose-dependent manner. Total protein O-GlcNAcylation showed the strongest correlation with Os IC50 (r = -0.73). Os synergized with regorafenib and the Os:Re combination inhibited growth of NCI-H508 tumor spheroids. These findings support OGT inhibition as a potential anticancer strategy and suggest total cellular O-GlcNAcylation as a predictive marker.

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CategoryResearch & Report

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Abstract

Introduction

PLOS ONE OPEN ACCESS Citation: Wongprayoon P, Pengnam S, Srisuphan R, Opanasopit P, Jirawatnotai S, Charoensuksai P (2024) The correlation between cellular O-GlcNAcylation and sensitivity to O-GlcNAc inhibitor in colorectal cancer cells. PLoS ONE 19(10): e0312173 . [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pone.0312173 Editor: Sadiq Umar, University of Illinois, UNITED STATES OF AMERICA Received: July 9, 2024 Accepted: October 2, 2024 Published: October 16, 2024 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: [https://doi.org/10.1371/journal.pone.0312173](https://doi.org/10.1371/journal.pone.0312173) [Copyright:](Copyright:) © [2024 Wongprayoon](2024 Wongprayoon) et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. RESEARCH ARTICLE The correlation between cellular O-GlcNAcylation and sensitivity to O-GlcNAc inhibitor in colorectal cancer cells Pawaris Wongprayoon1,2, Supusson Pengnam1,3,4, Roongtiwa Srisuphan2, Praneet Opanasopit3,4,5, Siwanon Jirawatnotai6,7,8, Purin Charoensuksai1,2 * 1 Faculty of Pharmacy, Department of Biomedicine and Health Informatics, Silpakorn University, Nakhon Pathom, Thailand, 2 Faculty of Pharmacy, Bioactives from Natural Resources Research Collaboration for Excellence in Pharmaceutical Sciences (BNEP), Silpakorn University, Nakhon Pathom, Thailand, 3 Faculty of Pharmacy, Center of Precision Medicine Innovation and Advanced Medicinal Product Development, Silpakorn University, Nakhon Pathom, Thailand, 4 Faculty of Pharmacy, Green Innovations Group (PDGIG), Silpakorn University, Nakhon Pathom, Thailand, 5 Faculty of Pharmacy, Department of Industrial Pharmacy, Silpakorn University, Nakhon Pathom, Thailand, 6 Faculty of Medicine Siriraj Hospital, Siriraj Center of Research Excellence for Precision Medicine and Systems Pharmacology, Mahidol University, Bangkok, Thailand, 7 Faculty of Medicine Siriraj Hospital, Department of Pharmacology, Mahidol University, Bangkok, Thailand, 8 Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand * [charoensuksai_p@su.ac.th](charoensuksai_p@su.ac.th) Abstract The upregulation of O-GlcNAc signaling has long been implicated in the development and progression of numerous human malignancies, including colorectal cancer. In this study, we characterized eight colorectal cancer cell lines and one non-cancerous cell line for OGlcNAc-related profiles such as the expression of OGT, OGA, and total protein O-GlcNAcylation, along with their sensitivity toward OSMI-1 (Os), an OGT inhibitor (OGTi) . Indeed, Os dose-dependently suppressed the viability of all colorectal cancer cell lines tested. Among the three O-GlcNAc profiles, our results revealed that Os IC50 exhibited the strongest correlation with total protein O-GlcNAcylation (Pearson Correlation Coefficient r = -0 .73), suggesting that total O-GlcNAcylation likely serves as a better predictive marker for OGTi sensitivity than OGT expression levels. Furthermore, we demonstrated that Os exhibited a synergistic relationship with regorafenib (Re) . We believed that this synergism could be explained, at least in part, by the observed Re-mediated increase of cellular O-GlcNAcylation, which was counteracted by Os. Finally, we showed that the Os:Re combination suppressed the growth of NCI-H508 tumor spheroids. Overall, our findings highlighted OGTi asa potential anticancer agent that could be used in combination with other molecul

FAQs

What cellular profiles were measured to assess O-GlcNAc-related characteristics in the colorectal cancer lines?

The study characterized OGT, OGA, and total protein O-GlcNAcylation profiles across eight colorectal cancer cell lines and one non-cancerous cell line.

How did OSMI-1 (Os) affect the viability of the colorectal cancer cell lines?

Os dose-dependently suppressed the viability of all colorectal cancer cell lines tested.

Which marker best predicted sensitivity to the OGT inhibitor Os?

Among the measured O-GlcNAc profiles, Os IC50 showed the strongest correlation with total protein O-GlcNAcylation, suggesting it is a better predictive marker than OGT expression.

Sep 21, 2026

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