Kim Dong-Il, Lee Tae-Kyun, Lim Ig-Seob, Kim Hwa, Lee Young-Choon, Kim Cheorl-Ho
Department of Biochemistry, Molecular Biology and Gynecology, Dongguk University School of Oriental Medicine and National Research Laboratory for Glycobiology, Sukjang-Dong 707, Kyungju City, Kyungbuk 780-714, Korea.
Toxicol Appl Pharmacol. 2005 Jun 15;205(3):213-24. doi: 10.1016/j.taap.2004.10.007.
Scutellaria barbata D. Don (Lamiaceae) (SB) is a perennial herb, which is natively distributed throughout Korea and southern China. This herb is known in traditional Chinese Medicine as Ban-Zhi-Lian and traditional Korean medicine as Banjiryun, respectively. SB has been used as an anti-inflammatory and antitumor agent. We aimed to determine the expression of growth factor molecules for growth inhibition after treatment of SB in two different human myometrial smooth muscle cell (SMC)s and leiomyomal SMCs. Water-soluble ingredients of SB, myometrial SMCs, and the leiomyomal cell lines were used in vitro. SB significantly reduced cell numbers in culture and arrested cell proliferation, and also induced apoptosis, indicating that the presence of an intact apoptotic pathway was demonstrated in these cells by SB. Uterine leiomyoma is the most common benign smooth muscle cell tumor of the myometrium. The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and leiomyomal cells with and without treatment with a water extract of SB for 3 days. IGF-I mRNA expression was significantly higher in leiomyomal cells than in myometrium cells. The IGF-I protein was more abundant in leiomyomal cells than in myometrium. When SB was treated to the cells, the IGF-I protein concentrations in myometrial and leiomyomal cells from the SB-treated cells were similar. The results indicated that IGF-I expression is probably associated with a proliferation of leiomyomal cells than myometrium. However, SB down-regulated the IGF-I expression where IGF-I contributes to the selective growth of the leiomyoma. Therefore, growth modulation of LMs by SB occurs via mechanisms dependent of apoptosis. The raw materials were extracted and subjected to functional isolation for the active molecules in the present assay systems. The five flavonoids were isolated and the chemical structures of resveratrol, baicalin, berberine, apigenin, and luteolin were determined. The effects of resveratrol, baicalin, and berberine on the above parameters have not been significantly evidenced, whereas apigenin and luteolin were effective. The anti-proliferative compounds apigenin and luteolin belong to the flavones, a class of flavonoids and are characterized as selectively inhibitors of the growth of LM cells. Our findings suggest that flavonoids of apigenin and luteolin are potentially useful for the development of therapeutic treatments of cancer. These data also suggest that SB reduces tumor volume with inducing a concomitant increase in the rate of apoptosis.
半枝莲（唇形科）是一种多年生草本植物，原产于韩国和中国南方。这种草药在传统中医中被称为半枝莲，在传统韩医中被称为반지르윤。半枝莲一直被用作抗炎和抗肿瘤药物。我们旨在确定在两种不同的人子宫肌层平滑肌细胞（SMC）和子宫肌瘤平滑肌细胞中，半枝莲处理后生长因子分子的表达情况，以实现生长抑制。半枝莲的水溶性成分、子宫肌层SMC和子宫肌瘤细胞系用于体外实验。半枝莲显著减少培养中的细胞数量并阻止细胞增殖，还诱导细胞凋亡，这表明半枝莲在这些细胞中证明了完整凋亡途径的存在。子宫肌瘤是子宫肌层最常见的良性平滑肌细胞肿瘤。在有或没有用半枝莲水提取物处理3天的子宫肌层和子宫肌瘤细胞中，检测胰岛素样生长因子-I（IGF-I）在mRNA和蛋白质水平的表达。IGF-I mRNA表达在子宫肌瘤细胞中显著高于子宫肌层细胞。IGF-I蛋白在子宫肌瘤细胞中比在子宫肌层中更丰富。当用半枝莲处理细胞时，来自半枝莲处理细胞的子宫肌层和子宫肌瘤细胞中的IGF-I蛋白浓度相似。结果表明，IGF-I表达可能与子宫肌瘤细胞而非子宫肌层细胞的增殖有关。然而，半枝莲下调了IGF-I的表达，而IGF-I有助于子宫肌瘤的选择性生长。因此，半枝莲对子宫肌瘤的生长调节是通过依赖凋亡的机制发生的。在本测定系统中，对原料进行提取并对活性分子进行功能分离。分离出了五种黄酮类化合物，并确定了白藜芦醇、黄芩苷、小檗碱、芹菜素和木犀草素的化学结构。白藜芦醇、黄芩苷和小檗碱对上述参数的影响尚未得到显著证实，而芹菜素和木犀草素是有效的。抗增殖化合物芹菜素和木犀草素属于黄酮类，是一类黄酮，其特征为子宫肌瘤细胞生长的选择性抑制剂。我们的研究结果表明，芹菜素和木犀草素类黄酮可能对癌症治疗的开发有用。这些数据还表明，半枝莲通过诱导凋亡率的同时增加来减少肿瘤体积。
