Zhao Wanzhou, Entschladen Frank, Liu Hongyan, Niggemann Bernd, Fang Qicheng, Zaenker Kurt S, Han Rui
Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No1 Xiannong Tan Street, Beijing 100050, China.
Cancer Detect Prev. 2003;27(1):67-75. doi: 10.1016/s0361-090x(02)00170-8.
The aim of the study was to investigate the antitumor and/or preventive effect of BC-4, an isomeric compound isolated from the plant Boswellia carteri Birdw. containing alpha- and beta-boswellic acid acetate in 1:1, MW 498.3. We used the MTT (3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide) assay to study the growth inhibition activity of BC-4. Tumor cells migration within a three-dimensional collagen matrix was recorded by time-lapse videomicroscopy and computer-assisted cell tracking. Topoisomerase II was isolated from mouse melanoma B16F10 cells and its activity was determined by its ability to cut plasmid pBR322 DNA. The secretion and activity of matrix metalloproteinases (MMPs) from human fibrosarcoma HT-1080 cells were determined by gelatin zymography. BC-4 was a cytostatic compound and could induce the differentiation of B16F10 mouse melanoma cells, blocked the cell population in G1 phase and inhibited topoisomerase II activity. The G1 phase population of B16F10 cells was increased from 57.4 to 87.7%, while S phase population was reduced from 33.3 to 5.9% after treatment with BC-4 at 25 microM concentration for 48 h. BC-4 also inhibited the migration activity of B16F10. BC-4 could induce apoptosis of HT-1080 cells, as proved by acridine orange fluorescence staining, Wright-Giemsa staining, electromicroscopy, DNA fragmentation and flow cytometry. BC-4 inhibited the secretion of MMPs from HT-1080 cells, too. In conclusion, if it turns out that BC-4 is a well tolerated substance, exhibiting no significant toxicity or side effects, being evaluated currently in China, BC-4 is a good candidate for the prevention of primary tumor, invasion and metastasis.
本研究的目的是调查BC - 4的抗肿瘤和/或预防作用。BC - 4是从植物乳香(Boswellia carteri Birdw.)中分离出的一种异构化合物,其含有比例为1:1的α - 和β - 乙酸乳香酸,分子量为498.3。我们使用MTT(3 -(4,5 - 二甲基噻唑 - 2 - 基)-2,5 - 二苯基四氮唑溴盐)法研究BC - 4的生长抑制活性。通过延时视频显微镜和计算机辅助细胞追踪记录肿瘤细胞在三维胶原基质中的迁移情况。从小鼠黑色素瘤B16F10细胞中分离拓扑异构酶II,并通过其切割质粒pBR322 DNA的能力来测定其活性。通过明胶酶谱法测定人纤维肉瘤HT - 1080细胞中基质金属蛋白酶(MMPs)的分泌和活性。BC - 4是一种细胞生长抑制剂,可诱导B16F10小鼠黑色素瘤细胞分化,使细胞群体阻滞于G1期并抑制拓扑异构酶II活性。在25微摩尔浓度下用BC - 4处理48小时后,B16F10细胞的G1期群体从57.4%增加到87.7%,而S期群体从33.3%减少到5.9%。BC - 4还抑制B16F10的迁移活性。吖啶橙荧光染色、瑞氏 - 吉姆萨染色、电子显微镜检查、DNA片段化和流式细胞术证明,BC - 4可诱导HT - 1080细胞凋亡。BC - 4也抑制HT - 1080细胞中MMPs的分泌。总之,如果BC - 4被证明是一种耐受性良好的物质,目前在中国正在进行评估,无明显毒性或副作用,那么BC - 4是预防原发性肿瘤、侵袭和转移的良好候选药物。