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Titolo:
Inhibition of potentially anti-apoptotic proteins by antisense protein kinase C-alpha (Isis 3521) and antisense bcl-2 (G3139) phosphorothioate oligodeoxynucleotides: Relationship to the decreased viability of T24 bladder andPC3 prostate cancer cells
Autore:
Benimetskaya, L; Miller, P; Benimetsky, S; Maciaszek, A; Guga, P; Beaucage, SL; Wilk, A; Grajkowski, A; Halperin, AL; Stein, CA;
Indirizzi:
Columbia Univ, Dept Pharmacol, New York, NY 10032 USA Columbia Univ New York NY USA 10032 ept Pharmacol, New York, NY 10032 USA Columbia Univ, Dept Med, New York, NY 10032 USA Columbia Univ New York NYUSA 10032 niv, Dept Med, New York, NY 10032 USA Johns Hopkins Univ, Dept Biochem, Baltimore, MD USA Johns Hopkins Univ Baltimore MD USA niv, Dept Biochem, Baltimore, MD USA Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA Johns Hopkins Univ Baltimore MD USA h Hyg & Publ Hlth, Baltimore, MD USA Polish Acad Sci, Ctr Mol & Macromol Studies, Dept Bioorgan Chem, Lodz, Poland Polish Acad Sci Lodz Poland l Studies, Dept Bioorgan Chem, Lodz, Poland US FDA, Div Therapeut Prot, Bethesda, MD 20014 USA US FDA Bethesda MD USA20014 , Div Therapeut Prot, Bethesda, MD 20014 USA
Titolo Testata:
MOLECULAR PHARMACOLOGY
fascicolo: 6, volume: 60, anno: 2001,
pagine: 1296 - 1307
SICI:
0026-895X(200112)60:6<1296:IOPAPB>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; FIBROBLAST GROWTH-FACTOR; STEREOCONTROLLED SYNTHESIS; GENE-EXPRESSION; FACTOR-BINDING; IN-VITRO; OLIGONUCLEOTIDES; INDUCTION; THERAPY; OVEREXPRESSION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Stein, CA Columbia Univ, Dept Pharmacol, 630 W 168th St, New York, NY 10032 USA Columbia Univ 630 W 168th St New York NY USA 10032 NY 10032 USA
Citazione:
L. Benimetskaya et al., "Inhibition of potentially anti-apoptotic proteins by antisense protein kinase C-alpha (Isis 3521) and antisense bcl-2 (G3139) phosphorothioate oligodeoxynucleotides: Relationship to the decreased viability of T24 bladder andPC3 prostate cancer cells", MOLEC PHARM, 60(6), 2001, pp. 1296-1307

Abstract

Isis 3521 and G3139 are 20- and 18-mer phosphorothioate oligonucleotides, respectively, targeted to the protein kinase C (PKC)-alpha and bcl-2 mRNAs. Treatment of T24 bladder and PC3 prostate carcinoma cells with full-lengthand 3'-truncation mutants of Isis 3521 causes down-regulation of PKC-a protein and mRNA. However, at the level of a 15-mer and shorter, downregulation of mRNA expression is no longer observed. Further, no diminution in cellular viability, as measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide assay, in response to increasing concentrations of paclitaxel, can be observed for these shorter oligomers. These observations not only indicate that PKC-alpha protein expression can be down-regulated by both RNase H-dependent and -independent mechanisms but also that down-regulationof PKC-alpha is insufficient by itself to "chemosensitize" cells. G3139, which down-regulates bcl-2 protein and mRNA expression, also down-regulates PKC-alpha protein and mRNA expression but not that of PKC-beta1, -epsilon, or -zeta. However, the down-regulation of PKC-alpha and bcl-2 are not linked. When the carrier Eufectin 5 is employed, only bcl-2 is down-regulated inboth T24 and PC3 cells at 50 nM oligonucleotide concentration. At 100 nM, both bcl-2 and PKC-alpha expression are down-regulated, and only at this concentration can "chemosensitization" to paclitaxel and carboplatin be observed. In contrast, the down-regulation of bcl-2 seems to be linked with thatof RelA (p65). However, this too is also not sufficient for chemosensitization, even though it leads to the loss of expression of genes under the putative control of nuclear factor-kappaB and to detachment of the cells from plastic surfaces. These results underscore the complexity of the intracellular requirements for the initiation of chemosensitization to anti-neoplastic agents.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 09:55:41