tris(2-pyridylmethyl)amine and Breast-Neoplasms

Berberine (BBR), an isoquinoline derivative alkaloid compound, has been reported to have anti-oxidant and anti-carcinogenic effects. A loss of functional p53 is involved with an increased risk of cancer proliferation and metastasis. Here, we investigated the effect of BBR on the transcriptional activity and the protein expression of p53 in p53-positive (wild- type, MCF7 cells) and p53-negative (mutant, MDA-MB231 cells) human breast cancer cells. Our results showed that the basal level of p53 mRNA and protein expression was increased by BBR treatment. However, tumor promoter, TPA, decreased the level of p53 mRNA and protein expression in MCF7 cells with wild-type p53. In addition, TPA-induced down-regulation of p53 mRNA and protein expression was increased by UO126, but not by SP600125 and SB203580. To verify the regulatory mechanism of p53 protein expression, we investigated the effects of proteasomal inhibitors (ALLN and MG132) or a lysosomal inhibitor (chloroquine) on TPA-induced down-regulation of p53. We observed that TPA-induced down-regulation of p53 protein was prevented by ALLN and MG132, but not by chloroquine. Further, we investigated the effect of BBR on TPA-induced down-regulation of p53 mRNA and protein levels. Interestingly, the levels of TPA-induced down-regulation of p53 mRNA and protein were prevented by BBR, but MDA-MB231 cells with mutated p53 were not affected. In addition, TPA-induced down-regulation of p53 mRNA was also prevented by BBR. Taken together, we suggest that BBR may be used as an effective ingredient for anticancer products, which trigger the transcriptional activity and the inhibition of the degradation of p53, a tumor suppressor gene, in human breast cancer.

Topics: Antineoplastic Agents; Berberine; Blotting, Western; Breast Neoplasms; Carcinogens; Cell Line, Tumor; Female; Gene Expression; Humans; Pyridines; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Suppressor Protein p53

Solanum nigrum L. (SNL) has been used in traditional folk medicine to treat numerous cancers. We isolated a glycoprotein (150 kDa) from SNL and tested its effect on the modulation of transcriptional factors (NF-kappa B and AP-1) and iNO production in TPA induced-MCF-7 cells, which are part of the human breast cancer cell line, without estrogen receptors. However, the mechanism of SNL glycoprotein in pharmacological and biochemical actions in cancer cells has not been studied. To test the effect of SNL glycoprotein on the DNA-binding activities of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), and nitric oxide (NO) production, these experiments were carried out using electrophoretic mobility shift assays (EMSA), western blot analysis, and the Griess method. Results in this experiment showed that SNL glycoprotein inhibits 12-O-Tetra decanoylphorbol-13-acetate (TPA; 100 nM)-induced DNA-binding activities of NF-kappaB and AP-1, and enhances NO production in MCF-7 cells. That is, our results indicated that SNL glycoprotein has the capacity to modulate the TPA-induced DNA-binding activities of transcription factors and NO production, which play a critical role with respect to cytotoxicity in MCF-7 cells. Therefore, SNL glycoprotein might be one of the agents that blocks TPA-mediated signal responses in tumor cells.

Topics: Breast Neoplasms; Carcinogens; DNA Adducts; Female; Glycoproteins; Humans; NF-kappa B; Nitric Oxide; Plant Extracts; Pyridines; Solanum nigrum; Tetradecanoylphorbol Acetate; Transcription Factor AP-1; Transcription, Genetic; Tumor Cells, Cultured