Thieno[2,3-b]pyridines as a Novel Strategy Against Cervical Cancer: Mechanistic Insights and Therapeutic Potential

Čikeš Botić, Monika; Marijan, Sandra; Radan, Mila; Novak, Ivana; Glumac, Mateo; Pilkington, Lisa I.; Odak, Zdravko; Barker, David; Reynisson, Jóhannes; Čikeš Čulić, Vedrana

Abstract

Cervical cancer is the fourth leading cause of cancer mortality in women worldwide, with limited therapeutic options for advanced or recurrent cases. In this study, the effects of a recent thieno[2,3-b]pyridine derivative, (E)-3-amino-5-(3-bromophenyl)acryloyl)-N-(3-chloro-2-methylphenyl)-6-methylthieno[2,3-b]pyridine-2-carboxamide (compound 1), on two cervical cancer cell lines, HeLa and SiHa, are investigated. Cytotoxicity was assessed by MTT assay, apoptosis rates were measured by flow cytometry, and metabolic profiling was performed by GC-MS. The study also examined the expression of eight glycosphingolipids (GSLs) in cancer stem cells (CSCs) and non-CSCs to assess glycophenotypic changes. Compound 1 showed significant cytotoxicity in both cell lines, with apoptosis identified as the primary mechanism of cell death. A significant reduction in the CSC population was observed, particularly in the SiHa cell line. Compound 1 treatment altered GSL expression and decreased GM2 levels in both CSCs and non-CSCs in the SiHa cell line and Gg3Cer levels in the HeLa cell line. Metabolic profiling identified 23 and 21 metabolites in the HeLa and SiHa cell lines, respectively, with significant differences in metabolite expression after treatment. These results underscore the potential of compound 1 as a promising therapeutic candidate for cervical cancer and warrant further investigation in preclinical and clinical settings.

Citation

Čikeš Botić, M., Marijan, S., Radan, M., Novak, I., Glumac, M., Pilkington, L. I., Odak, Z., Barker, D., Reynisson, J., & Čikeš Čulić, V. (in press). Thieno[2,3-b]pyridines as a Novel Strategy Against Cervical Cancer: Mechanistic Insights and Therapeutic Potential. International Journal of Molecular Sciences, 26(6), 1-24. https://doi.org/10.3390/ijms26062651

• Journal Article Type: Article
• Acceptance Date: Mar 11, 2025
• Online Publication Date: Mar 14, 2025
• Deposit Date: Apr 3, 2025
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 6
• Article Number: 2651
• Pages: 1-24
• DOI: https://doi.org/10.3390/ijms26062651
• Keywords: cervical cancer, cancer stem cells (CSCs), cytotoxicity, thieno[2,3-b]pyridines, apoptosis, glycosphingolipids (GSLs), metabolomics
• Public URL: https://keele-repository.worktribe.com/output/1112741