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Thieno[2,3-b]pyridines as a Novel Strategy Against Cervical Cancer: Mechanistic Insights and Therapeutic Potential
Monika Čikeš Botić1, Sandra Marijan2, Mila Radan3
1Department of Gynecology and Obstetrics, University Hospital of Split, 21000 Split, Croatia.
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.
Insights
A novel thienopyridine derivative, compound 1, effectively reduced cervical cancer cell viability and decreased cancer stem cells (CSCs). It induced apoptosis and altered glycosphingolipid profiles, showing therapeutic potential.
Area of Science:
- Oncology
- Medicinal Chemistry
- Biochemistry
Background:
- Cervical cancer is a leading cause of mortality in women globally.
- Limited therapeutic options exist for advanced or recurrent cervical cancer.
- Novel therapeutic agents are urgently needed.
Purpose of the Study:
- To investigate the anti-cancer effects of a novel thieno[2,3-b]pyridine derivative (compound 1) on cervical cancer cell lines.
- To evaluate compound 1's impact on cell viability, apoptosis, cancer stem cell populations, glycosphingolipid expression, and metabolic profiles.
- To assess the therapeutic potential of compound 1 for cervical cancer treatment.
Main Methods:
- Cytotoxicity assessed using MTT assay.
- Apoptosis rates measured by flow cytometry.
- Metabolic profiling conducted via Gas Chromatography-Mass Spectrometry (GC-MS).
- Glycosphingolipid (GSL) expression analyzed in cancer stem cells (CSCs) and non-CSCs.
Main Results:
- Compound 1 demonstrated significant cytotoxicity against HeLa and SiHa cervical cancer cell lines.
- Apoptosis was identified as the primary mechanism of cell death induced by compound 1.
- A notable reduction in CSC populations was observed, particularly in SiHa cells.
- Compound 1 altered GSL expression, decreasing GM2 and Gg3Cer levels in specific cell lines.
- Metabolic profiling revealed significant metabolite alterations post-treatment.
Conclusions:
- Compound 1 exhibits promising anti-cancer activity against cervical cancer cells.
- The compound's efficacy involves apoptosis induction and CSC reduction.
- Alterations in GSLs and metabolic profiles contribute to its anti-cancer effects.
- Compound 1 warrants further investigation as a potential therapeutic candidate for cervical cancer.
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