Notch2 activation is protective against anticancer effects of zerumbone in human breast cancer cells

被引：0
作者：
Anuradha Sehrawat
Kozue Sakao
Shivendra V. Singh
机构：
[1] University of Pittsburgh School of Medicine,Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute
[2] Kagoshima University,Department of Biochemical Science & Technology
来源：
Breast Cancer Research and Treatment | 2014年 / 146卷
关键词：
Zerumbone; Notch2; Presenilin-1; Apoptosis;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
We showed previously that zerumbone (ZER), a sesquiterpene isolated from subtropical ginger, inhibited in vitro (MCF-7 and MDA-MB-231cells) and in vivo (MDA-MB-231 cells) growth of human breast cancer cells in association with apoptosis induction. Here, we investigated the role of Notch receptors in anticancer effects of ZER (cell migration inhibition and apoptosis induction) using breast cancer cells. Western blotting was performed to determine protein expression changes. Effect of ZER on transcriptional activity of Notch was assessed by luciferase reporter assays. Transfection with small hairpin RNA or small interfering RNA was performed for knockdown of Notch2 or Presenilin-1 protein. Cell migration and apoptosis were quantitated by Boyden chamber assay and flow cytometry, respectively. Exposure of MDA-MB-231, MCF-7, and SUM159 cells to ZER resulted in increased cleavage of Notch2 in each cell line. On the other hand, levels of cleaved Notch1 and Notch4 proteins were decreased following ZER treatment. Increased cleavage of Notch2 in ZER-treated cells was accompanied by induction of Presenilin-1 protein and transcriptional activation of Notch. Inhibition of cell migration as well as apoptosis induction resulting from ZER exposure was significantly augmented by knockdown of Notch2 protein. ZER-mediated cleavage of Notch2 protein in MDA-MB-231 cells was markedly attenuated upon RNA interference of Presenilin-1. Knockdown of Presenilin-1 protein also resulted in escalation of ZER-induced apoptosis. The present study indicates that Notch2 activation by ZER inhibits its proapoptotic and anti-migratory response at least in breast cancer cells.
引用
收藏
页码：543 / 555
页数：12
相关论文
共 291 条
  • [11] Freedman AN(2001)Chemoprevention of azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from Life Sci 69 1935-1945
  • [12] van Duijn CM(2004)Zerumbone, a sesquiterpene in subtropical ginger, suppresses skin tumor initiation and promotion stages in ICR mice Int J Cancer 110 481-490
  • [13] Janssens AC(2009)Zerumbone, a tropical ginger sesquiterpene, inhibits colon and lung carcinogenesis in mice Int J Cancer 124 264-271
  • [14] Ellis MJ(2010)Regression of cervical intraepithelial neoplasia by zerumbone in female Balb/c mice prenatally exposed to diethylstilboestrol: involvement of mitochondria-regulated apoptosis Exp Toxicol Pathol 62 461-469
  • [15] Perou CM(2010)Potential chemoprevention of diethylnitrosamine-initiated and 2-acetylaminofluorene-promoted hepatocarcinogenesis by zerumbone from the rhizomes of the subtropical ginger ( Chem Biol Interact 186 295-305
  • [16] Siegel R(2002)) Carcinogenesis 23 795-802
  • [17] Naishadham D(2004)Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the α, β-unsaturated carbonyl group is a prerequisite FEBS Lett 572 245-250
  • [18] Jemal A(2005)Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes Oncogene 24 6957-6969
  • [19] Surh YJ(2007)Zerumbone abolishes NF-κB and IκBα kinase activation leading to suppression of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion Cancer Sci 98 118-126
  • [20] Singh SV(2007)Zerumbone, a bioactive sesquiterpene, induces G2/M cell cycle arrest and apoptosis in leukemia cells via a Fas- and mitochondria-mediated pathway Cancer Cell Int 3 4-1092
12345678910