Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Oncological Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of People's Republic of China, Xi'an, China.
Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Cancer Lett. 2012 Oct 1;323(1):48-57. doi: 10.1016/j.canlet.2012.03.037. Epub 2012 Apr 3.
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.
癌症干细胞（CSCs）参与前列腺癌（PCa）的发生和进展。传统的抗癌疗法未能根除 CSCs，这可能最终导致疾病复发和转移。因此，针对前列腺 CSCs 可能是治愈 PCa 的理想策略。染料木黄酮是大豆和豆制品中的主要异黄酮成分，已被证明对许多癌症具有强大的抗癌作用。我们之前曾报道过，染料木黄酮可以通过逆转上皮间质转化来抑制 PCa 细胞的侵袭，这表明染料木黄酮可能对转移性 PCa 有效。此外，我们最近还证明了前列腺癌肿瘤球细胞（TCs）具有 CSC 特性。在这里，我们发现染料木黄酮的存在明显抑制了 Pca 细胞的肿瘤球形成和集落形成。PCa TCs 的预处理也抑制了体内的致瘤性。此外，染料木黄酮处理还抑制了 PCa TCs 的肿瘤生长。进一步的研究表明，染料木黄酮治疗不仅导致体外和体内 PCa CSC 标志物 CD44 的下调，还抑制了 Hedgehog-Gli1 通路，这可能有助于染料木黄酮对 PCa TCs 的抗 CSC 作用。因此，我们的研究结果表明，染料木黄酮可能是一种具有靶向前列腺 CSCs 潜力的膳食植物化学物质。
