Kim Hyun A, Lee Dong-Sung, Lee Hwan, Lee Joomin
Department of Food and Nutrition Chosun University Gwangju Korea.
College of Pharmacy Chosun University Gwangju Korea.
Food Sci Nutr. 2020 Sep 10;8(10):5717-5728. doi: 10.1002/fsn3.1875. eCollection 2020 Oct.
Breast cancer is the most common cancer in women, and metastasis is the leading cause of death in breast cancer patients. Although chemoprevention is widely employed to treat breast cancer, anticancer drugs can cause significant adverse effects. Hance (LH) is a traditional Chinese medicinal plant with diverse therapeutic effects. However, its potential anticancer activity has not been fully investigated in breast cancers to date. Using high-performance liquid chromatography-mass spectrometry, we found that the main constituent of LH extract (LHE) was rutin. Our results indicated that LHE or rutin markedly decreased the proliferation and viability of estrogen receptor (ER)-positive MCF-7 and ER-negative HCC38 human breast cancer cells. LHE treatment induced morphological changes in apoptotic nuclei using 4',6-diamidino-2-phenylindole (DAPI) staining. Annexin V-fluorescein isothiocyanate (FITC) propidium iodide (PI) staining assay revealed that apoptosis significantly increased in both breast cancer cell types after LHE treatment. Additionally, the expression of poly (ADP-ribose) polymerase (PARP), Bcl-2, and phospho-Akt decreased, while that of cleaved PARP and p53 increased, in both cell types. Furthermore, LHE treatment inhibited epithelial-mesenchymal transition (EMT). LHE treatment significantly upregulated E-cadherin level in MCF-7 and HCC38 cells, while vimentin level was downregulated in HCC38 cells. In addition, transwell and wound-healing assays revealed that LHE or rutin inhibited breast cancer cell migration. Overall, these findings demonstrate that LHE is a promising therapeutic agent that acts by promoting apoptosis and reducing cell proliferation, EMT, and cell migration in ER-positive and ER-negative breast cancer cells.
乳腺癌是女性中最常见的癌症，转移是乳腺癌患者死亡的主要原因。尽管化学预防被广泛用于治疗乳腺癌，但抗癌药物会引起显著的不良反应。汉防己（LH）是一种具有多种治疗作用的传统中药。然而，其潜在的抗癌活性迄今尚未在乳腺癌中得到充分研究。通过高效液相色谱-质谱联用，我们发现LH提取物（LHE）的主要成分是芦丁。我们的结果表明，LHE或芦丁显著降低雌激素受体（ER）阳性的MCF-7和ER阴性的HCC38人乳腺癌细胞的增殖和活力。使用4',6-二脒基-2-苯基吲哚（DAPI）染色，LHE处理诱导凋亡细胞核出现形态变化。膜联蛋白V-异硫氰酸荧光素（FITC）碘化丙啶（PI）染色分析显示，LHE处理后两种乳腺癌细胞类型的凋亡均显著增加。此外，两种细胞类型中聚（ADP-核糖）聚合酶（PARP）、Bcl-2和磷酸化Akt的表达均降低，而裂解的PARP和p53的表达增加。此外，LHE处理抑制上皮-间质转化（EMT）。LHE处理显著上调MCF-7和HCC38细胞中E-钙黏蛋白水平，而波形蛋白水平在HCC38细胞中下调。此外，Transwell和伤口愈合分析显示，LHE或芦丁抑制乳腺癌细胞迁移。总体而言，这些发现表明，LHE是一种有前景的治疗药物，其作用机制是促进ER阳性和ER阴性乳腺癌细胞的凋亡，减少细胞增殖、EMT和细胞迁移。
