School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110006, PR China.
Department of Life Science and Biochemistry, Shenyang Pharmaceutical University, Shenyang, 110016, China.
J Ethnopharmacol. 2021 Sep 15;277:114057. doi: 10.1016/j.jep.2021.114057. Epub 2021 Mar 23.
Cimicifuga dahurica (Turcz.) Maxim (C. dahurica) has a long history of treating breast cancer. From the Qing Dynasty to the Tang Dynasty and even earlier, C. dahurica has been documented in the treatment of breast carbuncle (Breast cancer is classified as breast carbuncle in Chinese medicine). In traditional prescriptions such as "Sheng Ge Decoction", "Sheng Ma Powder" and "Breast Carbuncle Pill", as the main medicine, C. dahurica plays an important role. At present, the systematic studies on the in vitro and in vivo effects of Cimicifuga against breast cancer are rare, especially the C. dahurica.
In this article, we evaluated the in vitro activity and in vivo effects of CREE (extract of the root of C. dahurica) against breast cancer, and discussed the possible mechanism of CREE in promoting breast cancer cell apoptosis.
The main component in the CREE was analyzed by HPLC. The effects of CREE on the proliferation, migration and invasion of human breast cancer cells were evaluated through SRB, colony assay, LDH release, wound healing and transwell assay. The pro-apoptotic effect of CREE was investigated in Hochest33342 and Annexin V-FITC/PI assay. To verify the results of CREE in vivo effects, we applied nude mice subcutaneous xenograft experiments. The possible mechanism of CREE treating breast cancer was investigated through mitochondrial membrane potential and western blot experiments.
CREE contains cycloartane triterpene saponins. CREE can significantly inhibit the proliferation, migration and invasion of human breast cancer MCF-7 and MDA-MB-231 cells in vitro and it can effectively inhibit the growth of MDA-MB-231 cell subcutaneous tumors in vivo. Besides, we also found that CREE up-regulated the expression levels of Bax, caspase-9/3 and cytochrome C, and down-regulated the expression of Bcl-2. Therefore, regulation of the mitochondrial pathway may be one of the mechanisms by which CREE promotes breast cancer cell apoptosis.
CREE exhibits sufficient anti-breast cancer activity in vivo and in vitro, this study provides persuasive evidence for the further research and development of C. dahurica.
升麻属植物 dahurica(Turcz.)Maxim(C. dahurica)在治疗乳腺癌方面有着悠久的历史。从清朝到唐朝甚至更早,C. dahurica 就被记载于治疗乳痈(乳腺癌在中医中被归类为乳痈)的方剂中。在生葛汤、升麻散和乳痈丸等传统方剂中,C. dahurica 作为主要药物发挥着重要作用。目前,关于升麻属植物对乳腺癌的体外和体内作用的系统研究很少,特别是对 C. dahurica 的研究。
本文评估了 CREE(升麻属植物根提取物)对乳腺癌的体外活性和体内作用,并探讨了 CREE 促进乳腺癌细胞凋亡的可能机制。
采用 HPLC 分析 CREE 的主要成分。通过 SRB、集落形成实验、LDH 释放、划痕愈合和 Transwell 实验评估 CREE 对人乳腺癌细胞增殖、迁移和侵袭的影响。通过 Hochest33342 和 Annexin V-FITC/PI 实验研究 CREE 的促凋亡作用。为了验证 CREE 在体内作用的结果,我们应用裸鼠皮下异种移植实验。通过线粒体膜电位和 Western blot 实验研究 CREE 治疗乳腺癌的可能机制。
CREE 含有环阿尔廷三萜皂苷。CREE 能显著抑制人乳腺癌 MCF-7 和 MDA-MB-231 细胞的体外增殖、迁移和侵袭,有效抑制 MDA-MB-231 细胞皮下肿瘤的生长。此外,我们还发现 CREE 上调了 Bax、caspase-9/3 和细胞色素 C 的表达水平,下调了 Bcl-2 的表达水平。因此,调节线粒体途径可能是 CREE 促进乳腺癌细胞凋亡的机制之一。
CREE 在体内和体外均表现出足够的抗乳腺癌活性,本研究为进一步研究和开发升麻属植物提供了有说服力的证据。