Hu Enping, Wang Dongguo, Chen Jiayu, Tao Xiulin
Department of Urology, Taizhou Municipal Hospital 381 East Road of Zhongshan, Taizhou, Zhejiang 318000, PR China.
Department of Clinical Laboratory Medicine, Taizhou Municipal Hospital Affiliated with Taizhou University Taizhou 318000, Zhejiang, PR China.
Int J Clin Exp Med. 2015 Mar 15;8(3):4059-65. eCollection 2015.
Hedyotis diffusa is a well-known herb in traditional Chinese Medicine (TCM) which is used to treat various cancers including prostate cancer. Recently, lots of cyclotides possessing anti-cancer activities were found in Hedyotis family plants, suggesting that H.diffusa may also contain these bioactive ingredients. Cyclotides are heat-stable macrocyclic peptides from plants that display a wide range of biological activities. Currently, over 250 cyclotides have been discovered.
This study tried to isolate novel cyclotides from H.diffusa and further investigate their anti-cancer activities for the prostate cancer cells in vitro and in vivo.
The novel cyclotides from H.diffusa were isolated and purified by High-performance liquid chromatography (HPLC), amino acid sequences in their primary structure were confirmed using Edman degradation and gene cloning. Colorimetric cell viability assay (CCK8 assay), wound healing assay and human prostate cancer xenograft were used to analyze their anti-prostate cancer activity in vitro and in vivo.
Three novel cyclotides, termed as Diffusa cyclotide 1 to 3 (DC1-3) from the leaves and root of H.diffusa, were isolated firstly based on my knowledge. Using Edman degradation sequencing and gene cloning, we confirmed their amino acid sequence and obtained precursors of these peptides. By CCK8 assay, all present cyclotides showed potent cytotoxicity against all three prostate cancer cell lines, especially for DC3. In migration assay and wound healing assay, DC3 inhibited the cell migration and invasion Of LNCap cells. By model of prostate xenograft, DC3 could significantly inhibit development of the tumor in weight and size compared to the placebo.
The novel cyclotides extracted from H.Diffusa have anti-cancer effects, and they are potential bioactive ingredients in H.diffusa.
白花蛇舌草是一种著名的传统中药，用于治疗包括前列腺癌在内的各种癌症。最近，在白花蛇舌草属植物中发现了许多具有抗癌活性的环肽，这表明白花蛇舌草可能也含有这些生物活性成分。环肽是来自植物的热稳定大环肽，具有广泛的生物活性。目前，已发现超过250种环肽。
本研究试图从白花蛇舌草中分离新型环肽，并进一步研究其对前列腺癌细胞的体外和体内抗癌活性。
通过高效液相色谱（HPLC）从白花蛇舌草中分离纯化新型环肽，使用埃德曼降解法和基因克隆确定其一级结构中的氨基酸序列。采用比色法细胞活力测定（CCK8测定）、伤口愈合测定和人前列腺癌异种移植模型分析其体外和体内抗前列腺癌活性。
据我所知，首次从白花蛇舌草的叶和根中分离出三种新型环肽，命名为白花蛇舌草环肽1至3（DC1-3）。通过埃德曼降解测序和基因克隆，我们确定了它们的氨基酸序列，并获得了这些肽的前体。通过CCK8测定，所有现有的环肽对所有三种前列腺癌细胞系均显示出强大的细胞毒性，尤其是DC3。在迁移测定和伤口愈合测定中，DC3抑制了LNCap细胞的迁移和侵袭。通过前列腺异种移植模型，与安慰剂相比，DC3可显著抑制肿瘤的重量和大小发展。
从白花蛇舌草中提取的新型环肽具有抗癌作用，它们是白花蛇舌草中潜在的生物活性成分。
