Department of Breast Surgery, The First Affiliated Hospital of Jinzhou Medical University.
Medical College of Jinzhou Medical University.
Anticancer Drugs. 2023 Mar 1;34(3):373-383. doi: 10.1097/CAD.0000000000001462. Epub 2022 Nov 23.
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.
乳腺癌仍然是对女性健康的严重威胁，发现有效的治疗方法将有助于改善乳腺癌患者的预后。骆驼蓬碱是从骆驼蓬（Peganum harmala L.）中提取的，已被报道在几种恶性肿瘤中发挥肿瘤抑制活性。我们的目的是证明骆驼蓬碱对乳腺癌细胞恶性表型的影响。本研究采用乳腺癌细胞系（MDA-MB-231、SKBR3 和 MCF-7）和人正常乳腺细胞系 MCF-10A。MTT 和集落形成实验用于检测细胞活力和增殖。划痕愈合和 Transwell 实验用于评估骆驼蓬碱处理后细胞迁移和侵袭的变化。流式细胞术用于评估骆驼蓬碱诱导细胞凋亡的作用。此外，Western blot 实验用于检测上皮-间充质转化和磷脂酰肌醇 3 激酶（PI3K）信号通路的生物标志物。皮下植入检测肿瘤发生能力。骆驼蓬碱呈剂量依赖性抑制乳腺癌细胞的活力和增殖能力。流式细胞术显示骆驼蓬碱诱导 MCF-7 和 MDA-MB-231 细胞凋亡。此外，骆驼蓬碱有效抑制乳腺癌细胞的迁移和侵袭能力。Western blot 表明骆驼蓬碱显著促进 E-钙黏蛋白和 PTEN 表达，同时抑制 N-钙黏蛋白、波形蛋白、PI3K、p-mTOR 和 AKT 水平。通过 siRNA 干扰 PTEN 表达部分挽救了 PI3K 信号通路的活性。此外，骆驼蓬碱注射也抑制了乳腺癌细胞的肿瘤发生。我们的结果表明，骆驼蓬碱可以抑制多种恶性表型并抑制 PI3K 信号通路，这支持骆驼蓬碱可能是一种潜在的针对乳腺癌的肿瘤抑制天然化合物。
