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Titolo:
The differentiation inducers phenylacetate and phenylbutyrate modulate camptothecin sensitivity in colon carcinoma cells in vitro by intracellular acidification
Autore:
Cosentini, E; Haberl, I; Pertschy, P; Teleky, B; Mallinger, R; Baumgartner, G; Wenzl, E; Hamilton, G;
Indirizzi:
Univ Vienna, Sch Med, Dept Surg, Vienna, Austria Univ Vienna Vienna Austria Vienna, Sch Med, Dept Surg, Vienna, Austria Univ Vienna, Sch Med, Dept Histol & Embryol 2, Vienna, Austria Univ Vienna Vienna Austria ed, Dept Histol & Embryol 2, Vienna, Austria KH Lainz, Ludwig Boltzmann Inst Clin Oncol & Photodynam The, Vienna, Austria KH Lainz Vienna Austria st Clin Oncol & Photodynam The, Vienna, Austria
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 5, volume: 19, anno: 2001,
pagine: 1069 - 1074
SICI:
1019-6439(200111)19:5<1069:TDIPAP>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
MALIGNANT GLIOMAS; PH-REGULATION; ACIDIC PH; IN-VITRO; APOPTOSIS; INDUCTION; GROWTH; CANCER; CYTOTOXICITY; COMBINATION;
Keywords:
colon cancer; differentiation; phenylacetate; phenylbutyrate; camptothecin; intracellular pH;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
33
Recensione:
Indirizzi per estratti:
Indirizzo: Hamilton, G Univ Vienna, Surg Clin, Waehringer Guertel 18-20, A-1090 Vienna, Austria Univ Vienna Waehringer Guertel 18-20 Vienna Austria A-1090 ia
Citazione:
E. Cosentini et al., "The differentiation inducers phenylacetate and phenylbutyrate modulate camptothecin sensitivity in colon carcinoma cells in vitro by intracellular acidification", INT J ONCOL, 19(5), 2001, pp. 1069-1074

Abstract

Aromatic fatty acids such as phenylbutyrate (PB) and its metabolite phenylacetate (PA) induce growth arrest, differentiation and apoptosis in solid tumor cells. Despite their antiproliferative action they were reported to exhibit a synergistic effect in combination with cytotoxic drugs like topotecan, and others. Since the activity of the camptothecines (CPTs) depends on local pH conditions, we investigated, whether PB/PA modulate CPT effects indirectly by affecting intracellular pH in SW620 and SW480 colon cancer cells. The results for the colon carcinoma cells show an antagonistic interaction for the combination of CPT and 0.25-5 mM PA in viability assays, resulting in an approximately 3-fold increase in IC50 (control: 20 +/-7 nM). A synergistic effect with significantly increased numbers of late apoptotic/necrotic cancer cells (difference +21 +/-4%) and 1.4-fold sensitization were detected upon inclusion of 2.5 mM PA during a 4-h CPT (10 muM) loading phase. In response to 0.25-1 mM PA/PB the cells exhibit a reversible decrease of pHi (0.1-0.31 pH units) in HEPES- or bicarbonate-buffered media. Dose-dependent acidification and pHi-recovery occurred following addition of PA and PB after an acid load and inhibition of the Na+/H+-antiporter and bicarbonate exchangers, pointing to a possible intracellular mechanism of cytoplasmicacidification. It is concluded that the synergistic modulation of CPT toxicity by short-term PA/PB treatment in colon carcinoma cells is caused by changes in intracellular pH, possibly affecting, quantity and localization ofthe active closed lactone form of this drug.

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Documento generato il 29/03/20 alle ore 15:40:08