harmine and Carcinogenesis

Breast cancer remains a serious threaten to the women's health, discovery of potent treatment would help to improve the outcomes of breast cancer patients. Harmine extracted from Peganum harmala L , has been reported to exert tumor suppressive activity in several malignancies. Our objective was to demonstrate the effects of harmine on the malignant phenotypes of breast cancer cells. Breast cancer cell lines (MDA-MB-231, SKBR3, and MCF-7) and human normal breast cell line MCF-10A were employed in the present study. The MTT and colony formation assays were applied to the detection of cell viability and proliferation. Wound healing and transwell assays were performed to evaluate the alterations of cell migration and invasion after harmine treatment. Flow cytometry was applied to assess the effect of harmine in inducing cell apoptosis. Furthermore, western blotting assay was used to detect the biomarkers of epithelial-mesenchymal transition and phosphatidylinositol 3 kinase (PI3K) signaling pathway. The tumorigenesis ability was detected by subcutaneous implantation. Harmine dose-dependently suppressed the viability and proliferative capacity of breast cancer cells. Flow cytometry showed that harmine induced apoptosis in MCF-7 and MDA-MB-231 cells. In addition, harmine effectively inhibited the migration and invasion abilities of breast cancer cells. Western blotting indicated harmine significantly promoted E-cadherin and PTEN expression, while suppressed N-cadherin, vimentin, PI3K, p-mTOR, and AKT levels. Interfering the PTEN expression by siRNA partly rescued the activity of PI3K signaling pathway. Moreover, harmine injection also suppressed the tumorigenesis of breast cancer cells. Our results suggested that Hermine could suppress multiple malignant phenotypes and inhibit PI3K signaling, which supports that harmine might be a potential tumor-suppressive natural compound against breast cancer.

Topics: Apoptosis; Breast Neoplasms; Carcinogenesis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Harmine; Humans; Phenotype; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt

Numerous studies have shown that alteration of actin remodeling plays a pivotal role in the regulation of morphologic and phenotypic changes leading to malignancy. In the present study, we searched for drugs that can regulate actin polymerization and reverse the malignant phenotype in cancer cells. We developed a cell-free high-throughput screening assay for the identification of compounds that induce the actin polymerization in vitro, by fluorescence anisotropy. Then, the potential of the hit compound to restore the actin cytoskeleton and reverse the malignant phenotype was checked in EWS-Fli1-transformed fibroblasts and in B16-F10 melanoma cells. A β-carboline extracted from

Topics: Actin Cytoskeleton; Actins; Animals; Carcinogenesis; Cell Adhesion; Cell Death; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Shape; Fibroblasts; Fluorescence Polarization; Harmine; Humans; Melanoma, Experimental; Mice; NIH 3T3 Cells; Oncogene Proteins, Fusion; Phenotype; Polymerization; Proto-Oncogene Protein c-fli-1; RNA-Binding Protein EWS