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桑色素通过调节人乳腺癌细胞中Bax和Survivin的表达诱导细胞凋亡。

Morusin induces apoptosis by regulating expression of Bax and Survivin in human breast cancer cells.

作者信息

Kang Sukmin, Kim Eun-Ok, Kim Sung-Hoon, Lee Jun-Hee, Ahn Kwang Seok, Yun Miyong, Lee Seok-Geun

机构信息

Department of Cancer Preventive Material Development, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.

出版信息

Oncol Lett. 2017 Jun;13(6):4558-4562. doi: 10.3892/ol.2017.6006. Epub 2017 Apr 7.

Abstract

Morusin which has been isolated from the root bark of L. (Moraceae) has previously demonstrated anticancer activity in various types of cancer cells such as hepatocellular carcinoma, glioma and prostate cancer. However, the effect of morusin on breast cancer cells remains unclear. In the present study, the potential of morusin as an anti-cancer agent in breast cancer was investigated. The results of the present study revealed that the treatment of morusin induced cell death in various human breast cancer cell lines, but exhibited little effect on normal human breast epithelial cells. In Annexin V-propidium iodide double staining assays, morusin significantly increased apoptosis in a dose-dependent manner in human breast cancer cells. The apoptosis marker proteins cleaved caspase 3 and 9 were consistently upregulated following treatment of cells with morusin in a time- and dose-dependent manner. Furthermore, morusin was demonstrated to modulate the expression of the anti-apoptotic protein Survivin and pro-apoptotic protein B-cell lymphoma 2-associated-x protein (Bax) in human breast cancer cells. These results indicate that morusin induces apoptosis by suppressing Survivin and inducing Bax proteins, suggesting that morusin is a potentially effective therapeutic agent for the treatment of patients with breast cancer.

摘要

从桑科植物桑(Morus alba L.)根皮中分离得到的桑色素,此前已在多种癌细胞(如肝癌细胞、胶质瘤细胞和前列腺癌细胞)中显示出抗癌活性。然而,桑色素对乳腺癌细胞的作用仍不清楚。在本研究中,我们研究了桑色素作为乳腺癌抗癌剂的潜力。本研究结果表明,桑色素处理可诱导多种人乳腺癌细胞系发生细胞死亡,但对正常人乳腺上皮细胞影响很小。在膜联蛋白V-碘化丙啶双染试验中,桑色素在人乳腺癌细胞中以剂量依赖性方式显著增加细胞凋亡。在用桑色素处理细胞后,凋亡标记蛋白裂解的半胱天冬酶3和9以时间和剂量依赖性方式持续上调。此外,桑色素被证明可调节人乳腺癌细胞中抗凋亡蛋白Survivin和促凋亡蛋白B细胞淋巴瘤2相关X蛋白(Bax)的表达。这些结果表明,桑色素通过抑制Survivin和诱导Bax蛋白来诱导细胞凋亡,提示桑色素是治疗乳腺癌患者的一种潜在有效治疗剂。

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