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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 (8×60K 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: Kadioglu O

PROVIDER: S-ECPF-GEOD-64430 | biostudies-other | 2015 Feb

REPOSITORIES: biostudies-other

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Project description:We investigated the effect of high mobility group protein N2 (HMGN2) on the proliferation and apoptosis of the human MCF-7 breast cancer cell line, and its effect on tumor growth in a subcutaneous heterotopic transplantation tumor model of breast cancer. The cell viability assay was used to verify the effect of the recombinant human HMGN2 on MCF-7 cell proliferation. The Transwell chamber assay was used to verify the effect of HMGN2 on MCF-7 cell migration. Flow cytometry and Hoechst staining were used to detect the effect of HMGN2 on MCF-7 cell apoptosis. MCF-7 was injected to establish a subcutaneous heterotopic transplantation tumor model of breast cancer in nude mice. The size, weight and volume of tumor in each group were compared after the administration of different concentrations of HMGN2 solution around the tumor tissue at day 1, 3, 5 and 7. The tumor tissue was removed and cut into sections, and the apoptotic cells in tumors of nude mice were detected by a TUNEL kit. The CCK-8 assay showed that HMGN2 at different concentrations inhibited the proliferation of the MCF-7 breast cancer cells, and the proliferation of MCF-7 cells were significantly inhibited when the concentration of HMGN2 reached 3 µg/ml (P<0.01). The Transwell chamber assay showed that 3 µg/ml of HMGN2 significantly decreased the migration capacity of MCF-7 cells (P<0.01). Flow cytometry and Hoechst staining showed that 3 µg/ml of HMGN2 significantly increased apoptosis of MCF-7 cells (P<0.01). After the nude mouse model of breast cancer was established, HMGN2 at different concentrations was injected around the tumor tissue at day 1, 3, 5 and 7. We demonstrated that the growth of breast cancer was significantly inhibited when the concentration of HMGN2 reached 15 µg/ml. TUNEL staining showed that the number of apoptotic cells in the 15 µg/ml dose group was significantly higher than that in the control group (P<0.01). Therefore, in vitro and in vivo experiments proved that recombinant human HMGN2 could significantly inhibit the proliferation and migration of breast cancer cells, which increased the apoptosis of breast cancer cells and exerted anti-breast cancer effects, which enriched our understanding of the biological roles of HMGN2.

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

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