Epigallocatechin gallate inhibits sphere formation of neuroblastoma BE(2)-C cells
Epigallocatechin gallate inhibits sphere formation of neuroblastoma BE(2)-C cells
复制标题
DOI：
10.1007/s12199-011-0239-5
复制
发表时间：
2012-05-01
影响因子：
4.7
通讯作者：
Nishio, Hisahide
中科院分区：
文献类型：
--
作者：
Nishimura, Noriyuki;Hartomo, Tri Budi;Nishio, Hisahide
越来越多的流行病学研究表明，饮用绿色茶可以抑制多种癌症的生长。表没食子儿茶素没食子酸酯（EGCG）是绿色茶中含量最丰富的儿茶素，已被证明对许多癌症具有抗癌作用。大多数癌症被认为是由一小群肿瘤起始细胞（TIC）引发和维持的，这些肿瘤起始细胞（TIC）负责化疗耐药性和肿瘤复发。在神经母细胞瘤（一种经常复发且预后不良的侵袭性儿科肿瘤）中，TIC最近被鉴定为在用于神经嵴干细胞生长的无血清非贴壁培养物中生长的球体。尽管已有报道EGCG可诱导神经母细胞瘤细胞生长停滞和凋亡，但其对神经母细胞瘤TIC的影响仍有待确定。采用细胞计数、碘化丙啶染色、球化染色等方法检测EGCG对细胞增殖、凋亡和球化的影响。神经母细胞瘤BE（2）-C细胞显示干细胞标记物表达增加，（nanog同源框[NANOG]和八聚体结合转录因子4 [OCT 4]），以及与在常规培养中生长的亲本细胞相比，在无血清非贴壁培养中生长的球体中神经元分化标记物（Cu 2+转运ATP酶α多肽[ATP 7A]和dickkopf同源物2 [DKK 2]）的表达减少。虽然EGCG以剂量依赖性方式诱导亲本细胞的生长停滞和凋亡，但对球体无效。结果表明，EGCG可抑制BE（2）-C细胞中TIC的形成。
A growing number of epidemiological studies have demonstrated that the consumption of green tea inhibits the growth of a variety of cancers. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, has been shown to have an anti-cancer effect against many cancers. Most cancers are believed to be initiated from and maintained by a small population of tumor-initiating cells (TICs) that are responsible for chemotherapeutic resistance and tumor relapse. In neuroblastoma, an aggressive pediatric tumor that often relapses and has a poor prognosis, TICs were recently identified as spheres grown in a serum-free non-adherent culture used for neural crest stem cell growth. Although EGCG has been reported to induce growth arrest and apoptosis in neuroblastoma cells, its effect on neuroblastoma TICs remains to be defined.Gene expression was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The effects of EGCG on cell proliferation, apoptosis, and sphere formation were determined by cell counting, propidium iodide staining, and sphere (> 100 mu m in diameter) counting, respectively.Neuroblastoma BE(2)-C cells showed increased expression of stem cell markers (nanog homeobox [NANOG] and octamer-binding transcription factor 4 [OCT4]), as well as decreased expression of neuronal differentiation markers (Cu2+-transporting ATPase alpha polypeptide [ATP7A] and dickkopf homolog 2 [DKK2]) in spheres grown in serum-free non-adherent culture, compared to parental cells grown in conventional culture. Although EGCG induced growth arrest and apoptosis in the parental cells in a dose-dependent manner, it was not effective against spheres. However, EGCG potently inhibited sphere formation in the BE(2)-C cells.The present results suggest that EGCG may inhibit the development of TICs in BE(2)-C cells.