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Titolo:
Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappa B is enhanced by I kappa B alpha super-repressor and parthenolide
Autore:
Patel, NM; Nozaki, S; Shortle, NH; Bhat-Nakshatri, P; Newton, TR; Rice, S; Gelfanov, V; Boswell, SH; Goulet, RJ; Sledge, GW; Nakshatri, H;
Indirizzi:
Indiana Univ, Sch Med, Dept Surg, Indianapolis, IN 46202 USA Indiana UnivIndianapolis IN USA 46202 t Surg, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 ol Ctr, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA Indiana Univ Indianapolis IN USA 46202 Pathol, Indianapolis, IN 46202 USA Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USAIndiana Univ Indianapolis IN USA 46202 l Biol, Indianapolis, IN 46202 USA
Titolo Testata:
ONCOGENE
fascicolo: 36, volume: 19, anno: 2000,
pagine: 4159 - 4169
SICI:
0950-9232(20000824)19:36<4159:PSOBCC>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; KAPPA-B ACTIVATION; INDUCED APOPTOSIS; SESQUITERPENE LACTONE; NEGATIVE REGULATION; DRUG-RESISTANCE; KINASE COMPLEX; CYCLIN D1; EXPRESSION; INHIBITION;
Keywords:
breast cancer; parthenolide; paclitaxel; NF-kB;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
76
Recensione:
Indirizzi per estratti:
Indirizzo: Nakshatri, H Indiana Canc Res Inst, 1044 W Walnut St,R4-202, Indianapolis,IN 46202 USA Indiana Canc Res Inst 1044 W Walnut St,R4-202 Indianapolis INUSA 46202
Citazione:
N.M. Patel et al., "Paclitaxel sensitivity of breast cancer cells with constitutively active NF-kappa B is enhanced by I kappa B alpha super-repressor and parthenolide", ONCOGENE, 19(36), 2000, pp. 4159-4169

Abstract

The transcription factor nuclear factor-kappa B (NF-KB) regulates genes important for tumor invasion, metastasis and chemoresistance. Normally, NF-kappa B remains sequestered in an inactive state by cytoplasmic inhibitor-of-kappa B (I kappa B) proteins, NF-kappa B translocates to nucleus and activates gene expression upon exposure of cells to growth factors and cytokines,We and others have shown previously that NF-kappa B is constitutively active in a subset of breast cancers. In this study, we show that constitutive activation of NF-kappa B leads to overexpression of the antiapoptotic genesc-inhibitor of apoptosis 2 (c-IAP2) and manganese superoxide dismutase (Mn-SOD) in breast cancer cells, Furthermore, expression of the antiapoptotic tumor necrosis factor receptor associated factor 1 (TRAF1) and defender-against cell death (DAD-1) is regulated by NF-kappa B in certain breast cancercells. We also demonstrate that NF-kappa B-inducible genes protect cancer cells against paclitaxel as MDA-MB-231 breast cancer cells modified to overexpress I kappa B alpha required lower concentrations of paclitaxel to arrest at the G2/M phase of the cell cycle and undergo apoptosis when compared to parental cells. The effect of NF-kappa B on paclitaxel-sensitivity appears to be specific to cancer cells because normal fibroblasts derived from embryos lacking p65 subunit of NF-kappa B and wild type littermate embryos were insensitive to paclitaxel-induced G2/M cell cycle arrest. Parthenolide,an active ingredient of herbal remedies such as feverfew (tanacetum parthenium), mimicked the effects of I kappa B alpha by inhibiting NF-kappa B DNAbinding activity and Mn-SOD expression, and increasing paclitaxel-induced apoptosis of breast cancer cells. These results suggest that active ingredients of herbs with anti-inflammatory properties may be useful in increasingthe sensitivity of cancers with constitutively active NF-kappa B to chemotherapeutic drugs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 10/07/20 alle ore 19:10:00