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

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

  • PLoS One. 2024 Oct 16;19(10):e0312173. doi: 10.1371/journal.pone.0312173.
Pawaris Wongprayoon 1 2,  Supusson Pengnam 1 3 4,  Roongtiwa Srisuphan 2,  Praneet Opanasopit 3 4 5,  Siwanon Jirawatnotai 6 7 8,  Purin Charoensuksai 1 2
Affiliations

Affiliations

  • 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.
PMID: 39413067 DOI: 10.1371/journal.pone.0312173
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 O-GlcNAc-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 as a potential Anticancer agent that could be used in combination with Other molecules to enhance the efficacy while minimizing adverse effects, and identified total cellular O-GlcNAcylation as a potential predictive marker for OGTi sensitivity.

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