Cancer Letters, 2012, 323(1):48-57.

Genistein inhibits the stemness properties of prostate cancer cells through targeting Hedgehog–Gli1 pathway

Linlin Zhang, Lei Li, Min Jiao, et al

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, China

Cancer stem cells (CSCs) are involved in tumorigenesis and progression of prostate cancer (PCa). Conventional anticancer therapeutics failed to eradicate CSCs, which may eventually lead to the disease relapse and metastasis. Therefore, targeting prostate CSCs may be an ideal strategy to cure PCa. Genistein is a major isoflavone constituent of soybeans and soy products, which has been shown to exhibit potent anticancer effect on many cancers. We have previously reported that genistein can inhibit PCa cell invasion by reversing epithelial to mesenchymal transition, suggesting that genistein may be effective against metastatic PCa. In addition, we have recently demonstrated that PCa tumorsphere cells (TCs) possess CSC properties. Here, we found that tumorsphere formation and colony formation of Pca cells were noticeably suppressed in the presence of genistein. Pretreatment of PCa TCs with genistein also suppressed tumorigenicity in vivo. Additionally, genistein treatment inhibited tumor growth of PCa TCs. Further studies showed that genistein treatment not only led to the down-regulation of PCa CSC markers CD44 in vitro and in vivo, but also inhibited Hedgehog-Gli1 pathway, which may contribute to the anti-CSC effect of genistein in PCa TCs. Therefore, our findings demonstrated that genistein may be a dietary phytochemical with potential to target prostate CSCs.

爱尔兰《癌症快讯》，2012年10月

金雀异黄素通过靶向刺猬-Gli1 通路抑制前列腺癌细胞的干细胞特性

张琳琳，李磊，娇敏，等

中国西安交通大学第一附属医院泌尿外科

肿瘤干细胞 （CSCs） 参与了前列腺癌 (PCa)的发生和进展。传统抗癌疗法未能消除肿瘤干细胞，最终可能导致疾病复发和转移。因此，为前列腺癌肿瘤干细胞为靶标可能是治愈 PCa 的理想策略。金雀异黄素是大豆和大豆产物主要的异黄酮成分，已被证明对许多癌症具有强效抗癌作用。我们以前曾报道，金雀异黄素可以通过逆转上皮向间充质细胞转换抑制 PCa 细胞侵袭，表明金雀异黄素可有效抵御PCa转移 。此外，我们最近发现 PCa肿瘤球形细胞 (TCs) 拥有 CSC 的特性。在这里，我们发现在金雀异黄素明显抑制 了TCs的 形成和 PCa 细胞集落的形成。用金雀异黄素预处理PCa 的TCs也可在体内抑制裸鼠。此外，金雀异黄素治疗抑制了PCa TCs 的肿瘤生长。进一步研究表明，金雀异黄素治疗不仅导致了 PCa CSC 标记 物CD44 在体外和体内的下调，并且抑制了刺猬- Gli1 通路，这可能有助于金雀异黄素在 PCa TCs中发挥抗 CSC 的作用。因此，我们的研究结果表明，金雀异黄素可能是一种有潜力的抗前列腺肿瘤干细胞的饮食植物化学成分。