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

Autor: Odak Z; Department of Gynecology and Obstetrics, University Hospital of Split, 21000 Split, Croatia., Marijan S; Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia., Radan M; Department of Biochemistry, Faculty of Chemistry and Technology, University of Split, 21000 Split, Croatia., Pilkington LI; School of Chemical Sciences, The University of Auckland, Auckland 1010, New Zealand.; Te Pūnaha Matatini, Auckland 1010, New Zealand., Čikeš Botić M; Department of Gynecology and Obstetrics, University Hospital of Split, 21000 Split, Croatia., Barker D; School of Chemical Sciences, The University of Auckland, Auckland 1010, New Zealand.; The MacDiarmid Institute for Advanced Materials and Nanotechnology, Wellington 6140, New Zealand., Reynisson J; School of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, UK., Leung E; Faculty of Medical and Health Sciences, Auckland Cancer Society Research Centre, Auckland 1010, New Zealand., Čikeš Čulić V; Department of Medical Chemistry and Biochemistry, University of Split School of Medicine, 21000 Split, Croatia.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Jun 25; Vol. 25 (13). Date of Electronic Publication: 2024 Jun 25.
DOI: 10.3390/ijms25136954
Abstrakt: 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).
Databáze: MEDLINE