Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Zdravko Odak
* ORCID logo ,
Sandra Marijan
ORCID logo ,
Mila Radan
ORCID logo ,
Lisa I. Pilkington
ORCID logo ,
Monika Čikeš Botić
,
David Barker
ORCID logo ,
Jóhannes Reynisson
ORCID logo ,
Vedrana Čikeš-Čulić
ORCID logo
Version 1 : Received: 23 April 2024 / Approved: 24 April 2024 / Online: 24 April 2024 (10:06:01 CEST)

How to cite: Odak, Z.; Marijan, S.; Radan, M.; Pilkington, L.I.; Čikeš Botić, M.; Barker, D.; Reynisson, J.; Čikeš-Čulić, V. Deciphering the Interplay: Thieno[2,3-b]pyridine Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines. Preprints 2024, 2024041597. https://doi.org/10.20944/preprints202404.1597.v1 Odak, Z.; Marijan, S.; Radan, M.; Pilkington, L.I.; Čikeš Botić, M.; Barker, D.; Reynisson, J.; Čikeš-Čulić, V. Deciphering the Interplay: Thieno[2,3-b]pyridine Impact on Glycosphingolipid Expression, Cytotoxicity, Apoptosis, and Metabolomics in Ovarian Tumor Cell Lines. Preprints 2024, 2024041597. https://doi.org/10.20944/preprints202404.1597.v1

Abstract

Ovarian cancer is among the most common causes of female mortality. 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. Cytotoxicity, apoptosis, and metabolomic changes in ovarian cancer cell lines SK-OV-3 and OVCAR-3, as well as glycosphingolipid (GSL) expression, both 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 expression of eight GSLs on CSCs and non-CSCs was examined using flow cytometry. Both cell lines showed a change in the glycophenotype of the cells, either up or down of its expression, after the treatment. These findings raise the possibility of specifically targeting CSCs in ovarian cancer therapy. Additionally, treatment of Compound 1 resulted in a statistically significant increase in both early and late apoptosis (P<0.001) suggesting a pivotal role in initiating programmed cell death by the apoptotic pathway. The metabolic analysis revealed that the treated cancer cells showed reduced metabolic activity compared to the control group (P < 0.001)

Keywords

ovarian cancer, glycosphingolipids (GSLs), apoptosis, cytotoxicity, metabolomics, thieno[2,3-b]pyridine, cancer stem cells (CSCs)

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.