Department of Pharmaceutical Sciences, University of Calabria, 87036 Arcavacata di Rende, Cosenza, Italy.
J Ethnopharmacol. 2012 Mar 27;140(2):325-32. doi: 10.1016/j.jep.2012.01.022. Epub 2012 Jan 24.
Ziziphus extracts have been used in Traditional Chinese Medicine for the treatment of cancer.
In the present study we have investigated the effects of Ziziphus jujube extracts (ZEs) on breast cancer.
We evaluated the effects of increasing concentrations of ZEs on ERα positive MCF-7 and ERα negative SKBR3 breast cancer cell proliferation using MTT assays. Apoptosis was analyzed by evaluating the involvement of some pro-apoptotic proteins, including Bax, Bad, Bid and PARP cleavage by immunoblotting analysis. Moreover, the effects of ZEs treatment on apoptosis were tested by both DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. By using chromatographic techniques, we identified the constituents of the effective extracts.
ZE1, ZE2, and ZE4 exerted significant antiproliferative effects on estrogen receptor alpha (ERα) positive MCF-7 (IC(50) values of 14.42, 7.64, 1.69μg/mL) and ERα negative SKBR3 (IC(50) values of 14.06, 6.21, 3.70μg/mL) human breast cancer cells. Remarkably, ZEs did not affect cell viability of both normal human fibroblasts BJ1-hTERT and nonmalignant breast epithelial MCF-10A cells. Treatment with ZEs induced cell death by apoptosis in both malignant breast cells. We found that the most effective extracts ZE2 and ZE4 shared a number of triterpenic acids, already known for their anticancer activities.
Our data provide a rational base for the use of Ziziphus extracts in the treatment of breast cancer in Traditional Chinese Medicine.
酸枣仁提取物已在中国传统医学中用于治疗癌症。
本研究旨在探讨酸枣仁提取物（ZEs）对乳腺癌的作用。
我们通过 MTT 分析评估了增加 ZEs 浓度对 ERα 阳性 MCF-7 和 ERα 阴性 SKBR3 乳腺癌细胞增殖的影响。通过免疫印迹分析评估了一些促凋亡蛋白的参与，包括 Bax、Bad、Bid 和 PARP 切割，来分析细胞凋亡。此外，通过 DNA 片段化和末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）染色来测试 ZEs 处理对细胞凋亡的影响。通过色谱技术，我们鉴定了有效提取物的成分。
ZEs1、ZEs2 和 ZEs4 对雌激素受体α（ERα）阳性 MCF-7（IC50 值分别为 14.42、7.64 和 1.69μg/mL）和 ERα 阴性 SKBR3（IC50 值分别为 14.06、6.21 和 3.70μg/mL）人乳腺癌细胞具有显著的抗增殖作用。值得注意的是，ZEs 对正常人类成纤维细胞 BJ1-hTERT 和非恶性乳腺上皮 MCF-10A 细胞的细胞活力没有影响。ZEs 处理诱导两种恶性乳腺细胞发生细胞凋亡导致细胞死亡。我们发现，最有效的提取物 ZEs2 和 ZEs4 含有许多已被证实具有抗癌活性的三萜酸。
我们的数据为在传统中医中使用酸枣仁提取物治疗乳腺癌提供了合理的依据。
