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灯盏花乙素(BVP)通过调节微小染色体维持蛋白 7(MCM-7)损伤 DNA 抑制前列腺癌进展。

Breviscapine (BVP) inhibits prostate cancer progression through damaging DNA by minichromosome maintenance protein-7 (MCM-7) modulation.

机构信息

Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; Department of Urology, Affiliated Hospital of Nantong University, Nantong, 226001, China.

Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.

出版信息

Biomed Pharmacother. 2017 Sep;93:103-116. doi: 10.1016/j.biopha.2017.06.024. Epub 2017 Jun 17.

Abstract

Naturally occurring compounds are reported as effective candidates for prevention and treatment of various cancers. Breviscapine (BVP) is a mixture of flavonoid glycosides, derived from the Chinese herbs. Previous researches have indicated that BVP has comprehensive pharmacological functions. However, little is known about whether BVP has preventive effects on human prostate cancer. Here, we attempted to explore if BVP inhibits human prostate cancer in vitro and in vivo in a comprehensive manner. We found that BVP triggered cytotoxicity in prostate cancer cell lines dose-dependently. BVP-induced DNA damage caused the cell cycle arrest and apoptosis and further induced cell death. High expression of MCM-7 was reduced in BVP-treated cancer cells and tumor tissues, and also the DNA damage response marker of γH2AX is down-regulated by BVP, associated with MCM-7 expression through regulating retinoblastoma protein (Rb) and checkpoint control proteins expression. Additionally, BVP induced apoptotic response in prostate cancer cells and tumors via activating Caspase-3 and PARP. In vivo studies indicated that BVP impeded tumor growth in xenograft animal models. In conclusion, our data indicates that breviscapine (BVP) can be further explored for its potential, which might be used in human prostate cancer therapeutics.

摘要

天然存在的化合物被报道为预防和治疗各种癌症的有效候选物。灯盏花乙素(BVP)是一种黄酮苷混合物,来源于中国草药。先前的研究表明,BVP 具有广泛的药理作用。然而,目前还不清楚 BVP 是否对人类前列腺癌有预防作用。在这里,我们试图全面探讨 BVP 是否能在体外和体内抑制人类前列腺癌。我们发现 BVP 以剂量依赖的方式触发前列腺癌细胞系的细胞毒性。BVP 诱导的 DNA 损伤导致细胞周期停滞和细胞凋亡,并进一步诱导细胞死亡。BVP 处理的癌细胞和肿瘤组织中高表达的 MCM-7 减少,BVP 还下调了 DNA 损伤反应标志物 γH2AX,通过调节视网膜母细胞瘤蛋白(Rb)和检查点控制蛋白的表达与 MCM-7 表达相关。此外,BVP 通过激活 Caspase-3 和 PARP 在前列腺癌细胞和肿瘤中诱导凋亡反应。体内研究表明,BVP 抑制了异种移植动物模型中的肿瘤生长。总之,我们的数据表明,灯盏花乙素(BVP)可以进一步探索其在人类前列腺癌治疗中的潜力。

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