Srivastava Rakesh K, Tang Su-Ni, Zhu Wenyu, Meeker Daniel, Shankar Sharmila
Department of Pharmacology, Toxicology and Therapeutics, and Medicine, The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Front Biosci (Elite Ed). 2011 Jan 1;3(2):515-28. doi: 10.2741/e266.
According to the cancer stem cell hypothesis, the aggressive growth and early metastasis of cancer may arise through dysregulation of self-renewal of stem cells. The objectives of this study were to examine the molecular mechanisms by which sulforaphane (SFN, an active compound in cruciferous vegetables) inhibits self-renewal capacity of pancreatic cancer stem cells (CSCs), and synergizes with quercetin, a major polyphenol and flavonoid commonly detected in many fruits and vegetables. Our data demonstrated that SFN inhibited self-renewal capacity of pancreatic CSCs. Inhibition of Nanog by lentiviral-mediated shRNA expression enhanced the inhibitory effects of sulforaphane on self-renewal capacity of CSCs. SFN induced apoptosis by inhibiting the expression of Bcl-2 and XIAP, phosphorylation of FKHR, and activating caspase-3. Moreover, SFN inhibited expression of proteins involved in the epithelial-mesenchymal transition (beta-catenin, vimentin, twist-1, and ZEB1), suggesting the blockade of signaling involved in early metastasis. Furthermore, the combination of quercetin with SFN had synergistic effects on self-renewal capacity of pancreatic CSCs. These data suggest that SFN either alone or in combination with quercetin can eliminate cancer stem cell-characteristics.
根据癌症干细胞假说，癌症的侵袭性生长和早期转移可能源于干细胞自我更新的失调。本研究的目的是探讨萝卜硫素（SFN，十字花科蔬菜中的一种活性化合物）抑制胰腺癌干细胞（CSCs）自我更新能力的分子机制，以及与槲皮素协同作用的机制，槲皮素是许多水果和蔬菜中常见的一种主要多酚和类黄酮。我们的数据表明，SFN抑制了胰腺CSCs的自我更新能力。通过慢病毒介导的shRNA表达抑制Nanog可增强萝卜硫素对CSCs自我更新能力的抑制作用。SFN通过抑制Bcl-2和XIAP的表达、FKHR的磷酸化以及激活caspase-3来诱导细胞凋亡。此外，SFN抑制了参与上皮-间质转化的蛋白质（β-连环蛋白、波形蛋白、twist-1和ZEB1）的表达，提示其阻断了早期转移相关的信号传导。此外，槲皮素与SFN的组合对胰腺CSCs的自我更新能力具有协同作用。这些数据表明，SFN单独或与槲皮素联合使用均可消除癌症干细胞特性。
