Unknown,Transcriptomics,Genomics,Proteomics

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Effect of cajanin stilbene acid and its synthetic derivatives on MCF-7 breast cancer cells

ABSTRACT: Cajanin stilbene acid (CSA) was previously shown to induce cytotoxicity against cancer cells. We have employed microarray gene expression profiling to identify deregulated genes in MCF-7 breast cancer cells upon treatment with CSA and its synthetic derivatives (CSA6, CSA9, CSA19). TGM2 gene encoding transglutaminase 2 was commonly deregulated after treatment with all four CSA compounds. All compounds revealed strong effects on cell cycle progression and DNA damage response. Promoter motif analysis of the deregulated genes further supported the microarray results emphasizing the relevance of transcription factors regulating cell cycle and proliferation, MYC being among the most pronounced ones. Interestingly, cellular movement was among the top five affected cellular functions after treatment with the four derivatives. Gene expression profiling study with Whole Human Genome RNA chips (8M-CM-^W60K Agilent) was performed in MCF-7 breast cancer cells upon treatment with CSA and its synthetic derivatives (CSA6, CSA9, CSA19). Twelve chips were used; control (x2), CSA (x2), control (x2), CSA6 (x2), CSA9 (x2), CSA19 (x2). MCF-7 cells were treated with the compounds (IC50 concentrations) for 72 hours or left untreated (DMSO control). Two independent experiments were performed for each treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: Onat Kadioglu

PROVIDER: E-GEOD-64430 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells.

Kadioglu Onat O Fu Yujie Y Wiench Benjamin B Zu Yuangang Y Efferth Thomas T Efferth Thomas T

Archives of toxicology 20150226 3

In the present study, we investigated the activity and modes of action of cajanin stilbene acid (CSA) and its derivatives in terms of cytotoxicity, gene expression profile, and transcription factor activity. XTT assays on MCF7 cells were performed upon treatment with CSA or derivatives. After the determination of IC50 values, gene expression profiling was performed with Agilent microarray experiments. Deregulated genes were determined with Chipster software, pathway and functional analyses were ...[more]

PMID: 25716159

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Project description:Disseminated tumor cells (DTCs) in the bone marrow can be detected in patients with solid tumors early on in disease progression. Via interaction with mesenchymal stromal cells (MSCs) these tumor cells may interfere with hematopoiesis. Using appropriate co-culture models, we investigated whether DTCs can change the bone marrow microenvironment by modulating MSC function with a special emphasis on their chemoattractive activity towards hematopoietic stem and progenitor cells (HSPCs). Human bone marrow derived MSCs as well as an immortalised MSC line (SCP-1) were co-cultured with MCF-7, MDA-MB231 breast carcinoma or MCF-10A non-malignant breast epithelial cells or their conditioned medium. Gene expression analysis of SCP-1 cells cultured with MCF-7 conditioned medium revealed SDF-1/CXCL12 as one of the significantly downregulated genes. Both tumor cell lines caused an inhibited SDF-1 promoter activity in SCP-1 cells, whereby MCF-7 medium decreased it to 77% and MDA-MB231 to 47%. Moreover, the SDF-1 mRNA and protein levels were significantly reduced. As a functional consequence of lower SDF-1 levels, we detected a decreased trans-well migration potential of CD34+ HSPC to MSC/tumor cell co-cultures or conditioned medium. The specificity of this chemokine mediated effect was confirmed by blocking studies with the CXCR4 antagonist AMD3100. Downregulation of SP1 transcription factor and increased miR23a levels in MSCs after contact with tumor cell medium as well as an enhanced TGFb1 expression were identified as potential molecular regulators of SDF-1 activity in MSCs. We propose an additional mechanism by which tumor cells affect the niche environment of HSPCs and therefore negatively impact hematopoiesis. Gene expression of human immortalized mesenchymal stromal cells (SCP-1) was investigated after incubation with conditioned medium of the breast carcinoma cell line MCF-7 for 24, 48, and 72 hours. Three independent experiments were performed at each time.

Dataset Information

Effect of cajanin stilbene acid and its synthetic derivatives on MCF-7 breast cancer cells

Publications

Synthetic cajanin stilbene acid derivatives inhibit c-MYC in breast cancer cells.

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