Deciphering the Interplay: Thieno[2,3- b ]pyridine’s Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines

Odak, Zdravko; Marijan, Sandra; Radan, Mila; Pilkington, Lisa I.; Čikeš Botić, Monika; Barker, David; Reynisson, Jóhannes; Leung, Euphemia; Čikeš Čulić, Vedrana

Abstract

Ovarian cancer is among the most prevalent causes of mortality among women. Despite improvements in diagnostic methods, non-specific symptoms and delayed gynecological exams can lead to late-stage ovarian tumor discovery. In this study, the effect of an anti-cancer compound, 3-amino-N-(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3-b]quinoline-2-carboxamide (Compound 1), was examined. The impacts of cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, on cancer stem cells (CSCs), marked as CD49f+, and non-CSCs (CD49f−) were explored. Treatment with Compound 1 reduced the percentage of CSCs compared to non-treated cells (p < 0.001). The functional impact of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. The glycophenotype changed in both cell lines, with increases or decreases in its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment with Compound 1 resulted in statistically meaningful increased apoptosis, including both early and late apoptosis (p < 0.001), suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The analysis revealed that the metabolic activity of treated cancer cells was lower compared to those of the control group (p < 0.001).

Citation

Odak, Z., Marijan, S., Radan, M., Pilkington, L. I., Čikeš Botić, M., Barker, D., …Čikeš Čulić, V. (in press). Deciphering the Interplay: Thieno[2,3- b ]pyridine’s Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines. International Journal of Molecular Sciences, 25(13), Article 6954. https://doi.org/10.3390/ijms25136954

• Journal Article Type: Article
• Acceptance Date: Jun 19, 2024
• Online Publication Date: Jun 25, 2024
• Deposit Date: Jul 15, 2024
• Publicly Available Date: Jul 15, 2024
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 13
• Article Number: 6954
• DOI: https://doi.org/10.3390/ijms25136954
• Keywords: apoptosis, cytotoxicity, cancer stem cells (CSCs), thieno[2,3-b]pyridine, metabolomics, glycosphingolipids (GSLs), ovarian cancer
• Public URL: https://keele-repository.worktribe.com/output/875541