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Titolo:
Short exposure to millimolar concentrations of ethanol induces apoptotic cell death in multicellular HepG2 spheroids
Autore:
Castaneda, F; Kinne, RKH;
Indirizzi:
Max Planck Inst Mol Physiol, Abt Epithelphysiol, D-44227 Dortmund, GermanyMax Planck Inst Mol Physiol Dortmund Germany D-44227 7 Dortmund, Germany
Titolo Testata:
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
fascicolo: 6, volume: 126, anno: 2000,
pagine: 305 - 310
SICI:
0171-5216(200006)126:6<305:SETMCO>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
LASER-SCANNING MICROSCOPY; HEPATOCELLULAR-CARCINOMA; TUMOR SPHEROIDS; IN-VITRO; DOXORUBICIN; NECROSIS; ADRIAMYCIN; INDUCTION; VIABILITY; INJECTION;
Keywords:
ethanol; spheroids; cell viability; apoptosis; necrosis; hepatocellular carcinoma;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
32
Recensione:
Indirizzi per estratti:
Indirizzo: Castaneda, F Max Planck Inst Mol Physiol, Abt Epithelphysiol, Otto Hahn Str 11, D-44227Dortmund, Germany Max Planck Inst Mol Physiol Otto Hahn Str 11Dortmund Germany D-44227
Citazione:
F. Castaneda e R.K.H. Kinne, "Short exposure to millimolar concentrations of ethanol induces apoptotic cell death in multicellular HepG2 spheroids", J CANC RES, 126(6), 2000, pp. 305-310

Abstract

Purpose: We have shown previously that 1 mM ethanol reduces cell proliferation and increases apoptosis in monolayers of human hepatocellular carcinoma (HepG2) cells. However, in vivo liver tumors are usually three-dimensional and multicellular. The purpose of this study was therefore to determine the effect of ethanol in multicellular tumor spheroids (MCTS) as a model system in vitro. Methods: After the application of 1 mM ethanol for 24 h and 48 ht viable, apoptotic and necrotic cells within MCTS were stained with specific fluorescent dyes, and their amount and distribution within the MCTS were assessed by confocal laser scanning microscopy. To evaluate the effect on HepG2 cell migration and cell proliferation, the outgrowth potential after 1 week in culture was evaluated. Results: As assessed by YO-PRO-1 staining, ethanol increased the number of apoptotic cells from 21.5 units (U) in control spheroids to 364 U and 482.2 U after 24 h and 48 h in ethanol-treated spheroids, respectively (P < 0.001). Merocyanine staining fluorescence increased from 10.7 U in the control to 122 U after 24 h and 293.2 U after 48 h (P < 0.001). Cell viability, as determined by staining with the acetoxymethyl ester of calcein, decreased from 578.5 U in the control to 236 U and73.3 U after 24 h and 48 h of ethanol exposure respectively (P < 0.001). Necrosis showed an increase from 2 U in control to 24.9 after 24 h and 54 U after 48 h. MCTS treated with ethanol showed almost complete inhibition of outgrowth potential after 1 week in culture, compared to controls (P < 0.005). Conclusions: Small concentrations of ethanol (1 mM) induced apoptosis in HepG2 MCTS with a concomitant inhibition on outgrowth potential, accompanied with a low degree of necrosis. These findings suggest that low concentrations of ethanol may already be sufficient for the treatment of hepatocellular carcinoma.

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Documento generato il 04/12/20 alle ore 22:22:31