Concomitant inhibition of HSP90, its mitochondrial localized homologue TRAP1 and HSP27 by green tea in pancreatic cancer HPAF-II cells.
Concomitant inhibition of HSP90, its mitochondrial localized homologue TRAP1 and HSP27 by green tea in pancreatic cancer HPAF-II cells.
复制标题
DOI：
10.1002/pmic.201100242
复制
发表时间：
2011-12
期刊：
影响因子：
3.4
通讯作者：
Lu, Qing-Yi
中科院分区：
文献类型：
--
作者：
Zhang, Lifeng;Pang, Eric;Loo, Rachel R. Ogorzalek;Rao, Jianyu;Go, Vay-Liang W.;Loo, Joseph A.;Lu, Qing-Yi
胰腺癌是一种致命的疾病，其特点是预后不良和患者生存率低。绿茶多酚已被证明在多种癌症中表现出多种抗肿瘤活性，但对胰腺癌的研究非常有限。为了确定绿茶作用的细胞靶标，我们将绿茶提取物 (GTE) 暴露于人胰腺导管腺癌 HPAF-II 细胞，并对细胞裂解物进行二维凝胶电泳。我们鉴定出 32 种表达水平显着改变的蛋白质。这些蛋白质参与癌细胞的耐药性、基因调控、运动、解毒和代谢。特别是，我们发现 GTE 同时抑制分子伴侣热休克蛋白 90 (Hsp90)、其线粒体定位同源物 Hsp75（肿瘤坏死因子受体相关蛋白 1，或 Trap1）和热休克蛋白 27 (Hsp27)。 Western blot分析证实GTE抑制Hsp90、Hsp75和Hsp27，但增加Hsp27 Ser78的磷酸化。此外，我们发现 GTE 抑制 Akt 激活和突变 p53 蛋白的水平，并诱导细胞凋亡和生长抑制。我们的研究确定了 GTE 的多个新分子靶点，并为绿茶对胰腺癌的抗癌活性提供了进一步的证据。
Pancreatic cancer is a deadly disease characterized by poor prognosis and patient survival. Green tea polyphenols have been shown to exhibit multiple antitumor activities in various cancers, but studies on the pancreatic cancer are very limited. To identify the cellular targets of green tea action, we exposed a green tea extract (GTE) to human pancreatic ductal adenocarcinoma HPAF-II cells and performed two-dimensional gel electrophoresis of the cell lysates. We identified 32 proteins with significantly altered expression levels. These proteins are involved in drug resistance, gene regulation, motility, detoxification and metabolism of cancer cells. In particular, we found GTE inhibited molecular chaperones heat-shock protein 90 (Hsp90), its mitochondrial localized homologue Hsp75 (tumor necrosis factor receptor-associated protein 1, or Trap1) and heat-shock protein 27 (Hsp27) concomitantly. Western blot analysis confirmed the inhibition of Hsp90, Hsp75 and Hsp27 by GTE, but increased phosphorylation of Ser78 of Hsp27. Furthermore, we showed that GTE inhibited Akt activation and the levels of mutant p53 protein, and induced apoptosis and growth suppression of the cells. Our study has identified multiple new molecular targets of GTE and provided further evidence on the anticancer activity of green tea in pancreatic cancer.
登录
查看更多内容
影响因子：
4.8
作者：
Garneau, D;Revil, T;Chabot, B
通讯作者：
Chabot, B
影响因子：
3.5
作者：
Cross SE;Jin YS;Lu QY;Rao J;Gimzewski JK
通讯作者：
Gimzewski JK
影响因子：
2.9
作者：
Deer EL;González-Hernández J;Coursen JD;Shea JE;Ngatia J;Scaife CL;Firpo MA;Mulvihill SJ
通讯作者：
Mulvihill SJ
影响因子：
5.3
作者：
LAVOIE, JN;LAMBERT, H;LANDRY, J
通讯作者：
LANDRY, J
影响因子：
3.4
作者：
Lu, Qing-Yi;Yang, Yanan;Jin, Yu Sheng;Zhang, Zuo-Feng;Heber, David;Li, Frederick P.;Dubinett, Steven M.;Sondej, Melissa A.;Loo, Joseph A.;Rao, Jian Yu
通讯作者：
Rao, Jian Yu