Zhang Tingting, Fan Xinping, Song Lili, Ren Lu, Ma Enbo, Zhang Shengwan, Ren Liansheng, Zheng Yaowu, Zhang Jianzhen
Research Institute of Applied Biology, Shanxi University, Taiyuan, Shanxi, China.
IUBMB Life. 2015 Mar;67(3):175-81. doi: 10.1002/iub.1357. Epub 2015 Apr 11.
Crude brazilin extract from Sappan wood has demonstrated strong anti tumor activity in the mouse model of human bladder carcinoma and clinical trial for intravesical therapy. Purified brazilin was confirmed the most active molecule in inhibition of bladder carcinoma T24 cells. Brazilin decreased proliferation and viability of T24 cells in a dose- and time-dependent manner, with a calculated LC50 of 32 µg/mL. More than 1,000 of genes were found upregulated and down regulated by brazilin treatment in digital gene expression profiling. Gene ontology analysis indicated that stress response, apoptosis, and cell cycle regulatory pathways were highly enriched. Among the regulated genes, c-Fos was the most and specifically upregulated. Overexpression of c-Fos in T24 cells resulted in tumor cell specific changes in cell morphology and viability. Over expression of stress-responsive gene, HSP70, and other highly upregulated genes did not have any effect on cell growth. Brazilin may inhibit T24 cell growth and trigger cell death through a c-Fos-mediated and tumor cell specific signaling pathway. Further studies of its down stream mediators may help to identify better tumor cell type specific drug targets.
苏木中提取的粗巴西苏木精在人膀胱癌小鼠模型及膀胱内治疗的临床试验中已显示出强大的抗肿瘤活性。纯化后的巴西苏木精被确认为抑制膀胱癌细胞T24的最具活性的分子。巴西苏木精以剂量和时间依赖性方式降低T24细胞的增殖和活力，计算得出的半数致死浓度（LC50）为32 µg/mL。在数字基因表达谱分析中，发现有超过1000个基因在巴西苏木精处理后上调和下调。基因本体分析表明，应激反应、凋亡和细胞周期调控途径高度富集。在这些被调控的基因中，c-Fos上调最为显著且具有特异性。在T24细胞中过表达c-Fos会导致肿瘤细胞在细胞形态和活力方面发生特异性变化。应激反应基因HSP70及其他高度上调的基因的过表达对细胞生长没有任何影响。巴西苏木精可能通过c-Fos介导的、肿瘤细胞特异性的信号通路抑制T24细胞生长并引发细胞死亡。对其下游介质的进一步研究可能有助于确定更好的肿瘤细胞类型特异性药物靶点。
