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Titolo:
Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell lines through complex eicosanoid interactions
Autore:
Avis, I; Hong, SH; Martinez, A; Moody, T; Choi, YH; Trepel, J; Das, R; Jett, M; Mulshine, JL;
Indirizzi:
NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 ed Branch, Div Clin Sci, Bethesda, MD 20892 USA Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Pathol, Washington, DC 20307 USA Walter Reed Army Med Ctr Washington DC USA 20307 Washington, DC 20307 USA
Titolo Testata:
FASEB JOURNAL
fascicolo: 9, volume: 15, anno: 2001,
pagine: NIL_277 - NIL_306
SICI:
0892-6638(200107)15:9<NIL_277:FICMAI>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROLIFERATOR-ACTIVATED RECEPTORS; 5-LIPOXYGENASE-ACTIVATING PROTEIN FLAP; LEUKOTRIENE C-4 SYNTHASE; IN-VITRO GROWTH; PPAR-GAMMA; ARACHIDONIC-ACID; CYCLOOXYGENASE-2 EXPRESSION; PEROXISOME PROLIFERATORS; INFLAMMATORY RESPONSES; GENE-EXPRESSION;
Keywords:
breast cancer; leukotrienes; 5-lipoxygenase pathway; peroxisome proliferator-activated receptor; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
74
Recensione:
Indirizzi per estratti:
Indirizzo: Mulshine, JL NCI, Intervent Sect, CCB,MB, DCS,NIH,Clin Ctr, B10,12N226,9000 Rockville Pike, Bethesda, MD 20892 USA NCI B10,12N226,9000 Rockville PikeBethesda MD USA 20892 USA
Citazione:
I. Avis et al., "Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell lines through complex eicosanoid interactions", FASEB J, 15(9), 2001, pp. NIL_277-NIL_306

Abstract

Many arachidonic acid metabolites function in growth signaling for epithelial cells, and we previously reported the expression of the major arachidonic acid enzymes in human breast cancer cell lines. To evaluate the role of the 5-lipoxygenase (5-LO) pathway on breast cancer growth regulation, we exposed cells to insulinlike growth factor-1 or transferrin, which increased the levels of the 5-LO metabolite, 5(S)-hydrooxyeicosa-6E,8C,11Z,14Z-tetraenoic acid (5-HETE), by radioimmunoassay and high-performance liquid chromatography. Addition of 5-HETE to breast cancer cells resulted in growth stimulation, whereas selective biochemical inhibitors of 5-LO reduced the levelsof 5-HETE and related metabolites. Application of 5-LO or 5-LO activating protein-directed inhibitors, but not a cyclooxygenase inhibitor, reduced growth, increased apoptosis, down-regulated bcl-2, up-regulated bax, and increased G1 arrest. Exposure of breast cancer cells to a 5-LO inhibitor up-regulated peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma expression, and these same cells were growth inhibited when exposed to relevant PPAR agonists. These results suggest that disruption of the 5-LO signaling pathway mediates growth arrest and apoptosis in breast cancer cells. Additional experiments suggest that this involves the interplay of severalfactors, including the loss of growth stimulation by 5-LO products, the induction of PPAR gamma, and the potential activation of PPAR gamma by interactions with shunted endoperoxides.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/12/20 alle ore 07:43:34