Department of Pathology, New York University School of Medicine, New York, New York, USA.
Clin Cancer Res. 2011 Jul 1;17(13):4414-24. doi: 10.1158/1078-0432.CCR-11-0431. Epub 2011 May 23.
The development of new effective therapeutic agents with minimal side effects for prostate cancer (PC) treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine-Qing Dai (Indigo naturalis), has been used to treat leukemia for decades. However, the anticancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in PC.
The growth kinetics and invasion ability of on human PC cell lines with or without Natura-alpha treatment were measured by cell proliferation and invasion assays. The antitumor effects of Natura-alpha were examined in nude mice tumor xenograft models, and in a patient with advanced hormone-refractory metastatic PC. Signal network proteins targeted by Natura-alpha were analyzed by using proteomic pathway array analysis (PPAA) on xenografts.
Natura-alpha inhibited the growth of both androgen-dependent (LNCaP) and androgen-independent (LNCaP-AI, PC-3, and DU145) PC cells with IC(50) between 4 to 10 mmol/L, and also inhibited invasion of androgen-independent PC cells. Its antitumor effects were further evident in in vivo tumor reduction in androgen-dependent and androgen-independent nude mice tumor xenograft models and reduced tumor volume in the patient with hormone refractory metastatic PC. PPAA revealed that antiproliferative and antiinvasive activities of Natura-alpha on PC might primarily be through its downregulation of Forkhead box M1 (FOXM1) protein. Forced overexpression of FOXM1 largely reversed the inhibition of growth and invasion by Natura-alpha.
Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone-sensitive and hormone-refractory PC with minimal side effects.
开发具有最小副作用的新型有效治疗药物，以治疗前列腺癌（PC），这是非常必要的。靛玉红是一种从传统中药-青黛（天然靛蓝）中提取的活性分子，已被用于治疗白血病数十年。然而，Natura-alpha（靛玉红的一种衍生物）在实体瘤，特别是 PC 中的抗癌特性尚未得到很好的研究。
通过细胞增殖和侵袭实验测量 Natura-alpha 处理前后人 PC 细胞系的生长动力学和侵袭能力。在裸鼠肿瘤异种移植模型和晚期激素难治性转移性 PC 患者中，检查了 Natura-alpha 的抗肿瘤作用。通过使用异种移植中的蛋白质组学途径分析（PPAA）分析 Natura-alpha 靶向的信号网络蛋白。
Natura-alpha 抑制了依赖雄激素（LNCaP）和非依赖雄激素（LNCaP-AI、PC-3 和 DU145）PC 细胞的生长，IC（50）在 4 至 10mmol/L 之间，并且还抑制了非依赖雄激素的 PC 细胞的侵袭。其在依赖雄激素和非依赖雄激素的裸鼠肿瘤异种移植模型中的抗肿瘤作用进一步明显，并且降低了激素难治性转移性 PC 患者的肿瘤体积。PPAA 表明，Natura-alpha 对 PC 的抗增殖和抗侵袭作用主要可能是通过下调叉头框 M1（FOXM1）蛋白。FOXM1 的强制过表达在很大程度上逆转了 Natura-alpha 对生长和侵袭的抑制作用。
Natura-alpha 可以作为一种新型有效的治疗药物，用于治疗激素敏感和激素难治性 PC，副作用最小。
