Nutrition & Cancer, 2010, 62(6):795-801.

Protection of p53 wild type cells from taxol by genistein in the combined treatment of lung cancer

Sergey V. Tokalov, Andrij M. Abramyuk, and Nasreddin D. Abolmaali

Dresden University of Technology, Dresden, Germany

This study specifies the basic principles to selectively kill p53-deficient cells (H1299, FaDu) by taxol and to protect p53 wild type cells (A549) by the prior administration of structurally related flavonoids (apigenin, genistein, and quercetin). Cytotoxic and cytostatic properties of flavonoids were investigated in vitro by flow cytometry and were compared to known anticancer drugs (cisplatin, doxorubicin, etoposide). It was confirmed that doxorubicin induced growth arrest and protected A549 cells from taxol while simultaneously killing or blocking H1299 and FaDu cancer cells. It was found that doxorubicin could be successfully substituted in this way by the isoflavone genistein used at physiologically relevant concentrations. The other compounds analyzed revealed less selectivity (apigenin, cisplatin) or demonstrated higher toxicity (cisplatin, etoposide, and quercetin). We concluded that genistein-based therapy may have antagonistic effects when combined with mitotic poisons. The proposed therapeutic strategy allows protection of p53 wild type cells from taxol and selectively increases apoptosis in p53-deficient cells. This strategy exploits the naturally occurring compound that can be used without significant toxicity in rather high concentrations as present in common diets.

美国《营养和癌症》2010年7月

在联合治疗肺癌时金雀异黄素可以保护从紫杉醇中提取的P53型野生细胞

谢尔盖 V 唐纳德，安德鲁 M 阿布拉缪克和纳斯 D 阿波玛丽

德国德累斯顿技术大学

这项研究指定的基本原则是利用紫杉醇选择性杀死 p53 缺陷细胞 （H1299 ,FaDu），并且通过预先添加的结构上相似的黄酮类化合物 （芹菜、金雀异黄素和槲皮素）来保护 p53 型野生细胞 (A549)。采用体外流式细胞术探究黄酮类化合物的细胞毒性和细胞生长抑制性能，并且与已知的抗癌药物 （顺铂、 阿霉素、 足叶乙甙）进行对照。已经证实，阿霉素可以诱导生长抑制和保护紫杉醇的A549 细胞，并且同时杀死或阻塞 H1299 细胞和FaDu癌细胞。我们还发现在这一方面处于生理浓度的异黄酮金雀异黄素可以成功地替代阿霉素。其他化合物的分析显示出较少的选择性 （芹菜素，顺铂） 或表现出较高的毒性 （顺铂、 依托泊苷 和槲皮素）。我们可以得出结论，当与有丝分裂的毒素共用时基于金雀异黄素的疗法可能有拮抗作用。拟定的治疗策略允许保护紫杉醇的p53 野生型细胞，并且选择性地促进 p53 缺陷细胞的凋亡。这一方法利用自然形成的化合物，在日常的饮食中以相当高的浓度使用并且没有明显的毒性。