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.