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

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- -(3-chloro-2-me...

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Veröffentlicht in:International journal of molecular sciences 2024-07, Vol.25 (13), p.6954
Hauptverfasser: Odak, Zdravko, Marijan, Sandra, Radan, Mila, Pilkington, Lisa I, Čikeš Botić, Monika, Barker, David, Reynisson, Jóhannes, Leung, Euphemia, Čikeš Čulić, Vedrana
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container_issue 13
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container_title International journal of molecular sciences
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creator Odak, Zdravko
Marijan, Sandra
Radan, Mila
Pilkington, Lisa I
Čikeš Botić, Monika
Barker, David
Reynisson, Jóhannes
Leung, Euphemia
Čikeš Čulić, Vedrana
description 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- -(3-chloro-2-methylphenyl)-5-oxo-5,6,7,8-tetrahydrothieno[2,3- ]quinoline-2-carboxamide (Compound ), 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 reduced the percentage of CSCs compared to non-treated cells ( < 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 resulted in statistically meaningful increased apoptosis, including both early and late apoptosis ( < 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 ( < 0.001).
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subjects Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Cell death
Cell Line, Tumor
Cytotoxicity
Female
Glycosphingolipids - metabolism
Gynecology
Humans
Kinases
Metabolome - drug effects
Metabolomics - methods
Neoplastic Stem Cells - drug effects
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Ovarian cancer
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Pyridines - pharmacology
Statistical significance
Stem cells
Tumors
title Deciphering the Interplay: Thieno[2,3- b ]pyridine's Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines
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