Dataset Information

Investigating the multi-mechanistic anticancer effects of 4-bisarylurea thiouracil derivatives in breast cancer cells

ABSTRACT: The study reports the synthesis of a series of 4-bisarylureathiouracil derivatives (6a-e) for potential use in breast cancer treatment. In vitro cytotoxicity was assessed in MCF-7 and MDA-MB-231 human breast cancer cell lines, revealing significant anti-cancer activity. Compound 6e exhibited the highest cytotoxicity, with IC50 values of 7.94 μM for MCF-7 and 6.67 μM for MDA-MB-231, although it was also the most toxic to RAW 264.7 macrophage cells. In contrast, compound 6c demonstrated strong efficacy against both cancer cell lines (IC50 = 9.23 ± 0.6 μM for MCF-7 and 7.72 ± 0.6 μM for MDA-MB-231) while maintaining selectivity (SI values >10.8 and > 12.9, respectively). Flow cytometry and caspase-3 assays indicated that compounds 6a-c induced apoptosis in MCF-7 cells. In anti-inflammatory assays, compounds 6a and 6d showed significant effects, while 6c demonstrated the weakest, suggesting its cytotoxicity is not linked to anti-inflammatory properties. Compound 6c was prioritised for further investigation because of its preferential targeting of cancer cells. Proteomic analysis of 6c-treated cells revealed significant dysregulation of apoptosis, angiogenesis and VEGF signalling, Rho signal transduction, and pi3k-akt signalling pathways. These findings highlighted the potential of compounds 6a-e as effective anticancer agents, warranting further investigation and optimization for therapeutic applications.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Breast Cancer

SUBMITTER: Muhammad Alsherbiny

LAB HEAD: Mohamed Fares

PROVIDER: PXD065576 | Pride | 2025-07-19

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	MF3.DerivedFromSearchb0859911-48c1-4ca0-8415-0aa80d3823d0.mgf	Mgf
	MF3.mzid	Mzid
	MF3.zip	Other
	PQIP_Abundance_Control_C_vsTreatment_MF3.csv	Csv
	QC.pdf	Pdf

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Publications

Investigating the multi-mechanistic anticancer effects of 4-bisarylurea thiouracil derivatives in breast cancer cells.

Fares Mohamed M Alsherbiny Muhammad M Elkelesh Islam A IA Said Mohamed A MA Maklad Raed M RM Lewis William W Li Chun Guang CG Eldehna Wagdy M WM Groundwater Paul W PW Gale Philip A PA Keller Paul A PA

Bioorganic chemistry 20250511

The study reports the synthesis of a series of 4-bisarylureathiouracil derivatives (6a-e) for potential use in breast cancer treatment. In vitro cytotoxicity was assessed in MCF-7 and MDA-MB-231 human breast cancer cell lines, revealing significant anti-cancer activity. Compound 6e exhibited the highest cytotoxicity, with IC<sub>50</sub> values of 7.94 μM for MCF-7 and 6.67 μM for MDA-MB-231, although it was also the most toxic to RAW 264.7 macrophage cells. In contrast, compound 6c demonstrated ...[more]

PMID: 40412224

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Project description:The long-term goal of our study is to understand the genetic and epigenetic mechanisms of breast cancer metastasis in human and to discover new possible genetic markers for use in clinical practice. We have used microarray technology (Human OneArray microarray, phylanxbiotech.com) to compare gene expression profiles of non-invasive MCF-7 and invasive MDA-MB-231 cells exposed to dioscin (DS), a steroidal saponin isolated from the roots of wild yam, (Dioscorea villosa). Initially the differential expression of genes (DEG) was identified that followed pathway enrichment analysis (PEA). Of the genes queried on OneArray, we identified 4641 DEG changed between MCF-7 and MDA-MB-231 cells (vehicle-treated) with cut-off log2 |fold change|â§ 1. Among these genes, 2439 genes are upregulated and 2002 genes are downregulated. DS exposure (2.30 ïM, 72 h) to these cells identified 801 (MCF-7) and 96 (MDA-MB-231) DEG that showed significant difference compared to untreated cells (p<0.05). Within these gene sets, DS is able to upregulate 395 genes and downregulate 406 genes in MCF-7 and upregulate 36 and downregulate 60 genes in MDA-MB-231 cells. Further comparison of DEG between MCF-7 and MDA-MB-231 cells exposed to DS identified 3626 DEG of which 1700 were upregulated and 1926 genes were down-regulated. From PEA, 12 canonical pathways were significantly altered between these two cell lines (MCF-7 and MDA-MB-231). However, no alteration in any of these pathways was noticed in MCF-7 cell, while in MDA-MB-231 cells only MAPK pathway showed significant alteration. When PEA comparison was made on DS exposed cells, it was observed that only 2 pathways were significantly affected. Further, to identify shared DEG, which are targeted by DS and overlapped in both MCF-7 and MDA-MB-231 cells, we performed intersection analysis (Venn diagram). We found that only 7 DEG are overlapped of which six are reported in the database. This study highlights the diverse gene networks and pathways through which DS exhibits its effect on breast cancer cells. Two condition experiment. Human breast cancer Cell line MCF-7 groups: Vehicle control and dioscin treated; Human breast cancer cell line MDA-MB-231 cell group; vehicle control and dioscin-treated. Biological replicates: MCF-7 control compared to MCF-7 dioscin treated; MDA-MB-231 control compated to MDA-MB-231 dioscin-treated; MCF-7 control compared to MDA-MB-231 control; MCF-7 dioscin treated compared to MDA-MB-231 dioscin-treated. duplicate array

Project description:The long-term goal of our study is to understand the genetic and epigenetic mechanisms of breast cancer metastasis in human and to discover new possible genetic markers for use in clinical practice. We have used microarray technology (Human OneArray microarray, phylanxbiotech.com) to compare gene expression profiles of non-invasive MCF-7 and invasive MDA-MB-231 cells exposed to dioscin (DS), a steroidal saponin isolated from the roots of wild yam, (Dioscorea villosa). Initially the differential expression of genes (DEG) was identified that followed pathway enrichment analysis (PEA). Of the genes queried on OneArray, we identified 4641 DEG changed between MCF-7 and MDA-MB-231 cells (vehicle-treated) with cut-off log2 |fold change|≧ 1. Among these genes, 2439 genes are upregulated and 2002 genes are downregulated. DS exposure (2.30 M, 72 h) to these cells identified 801 (MCF-7) and 96 (MDA-MB-231) DEG that showed significant difference compared to untreated cells (p<0.05). Within these gene sets, DS is able to upregulate 395 genes and downregulate 406 genes in MCF-7 and upregulate 36 and downregulate 60 genes in MDA-MB-231 cells. Further comparison of DEG between MCF-7 and MDA-MB-231 cells exposed to DS identified 3626 DEG of which 1700 were upregulated and 1926 genes were down-regulated. From PEA, 12 canonical pathways were significantly altered between these two cell lines (MCF-7 and MDA-MB-231). However, no alteration in any of these pathways was noticed in MCF-7 cell, while in MDA-MB-231 cells only MAPK pathway showed significant alteration. When PEA comparison was made on DS exposed cells, it was observed that only 2 pathways were significantly affected. Further, to identify shared DEG, which are targeted by DS and overlapped in both MCF-7 and MDA-MB-231 cells, we performed intersection analysis (Venn diagram). We found that only 7 DEG are overlapped of which six are reported in the database. This study highlights the diverse gene networks and pathways through which DS exhibits its effect on breast cancer cells.