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標題: ATP depletion is an important factor in DHEA-induced growth inhibition and apoptosis in BV-2 cells
作者: Yang, N.C.
Jeng, K.C.G.
Ho, W.M.
Hu, M.L.
關鍵字: DHEA;antproliferation;apoptosis;ATP depletion;colonic adenocarcinoma cells;dehydroepiandrosterone-sulfate;oxidative;stress;cycle arrest;glucose-6-phosphate-dehydrogenase;rats;proliferation;steroids;2',7'-dichlorofluorescin;hepatocytes
Project: Life Sciences
期刊/報告no:: Life Sciences, Volume 70, Issue 17, Page(s) 1979-1988.
Dehydroepiandrosterone (DHEA), a major steroid secreted by the adrenal gland, is known to have antiproliferative effects but the mechanism is unclear. We recently reported that DHEA induces growth inhibition and apoptosis in BV-2 cells and these effects are inversely associated with glucose concentrations in the medium. Here, we further showed that incubation of BV-2 cells with DHEA under glucose deprivation (GO) led to dose- and time-dependent decrease in cellular ATP levels. The decrease in ATP preceded growth inhibition and apoptosis induced by DHEA and all these effects of DHEA (i.e., loss of ATP, antiproliferation and apoptosis) were prevented by glucose added at 4.5 mg/ml (G4.5) during incubation. In addition, two ATP-depleting agents, iodoacetic acid (IAA) and 2,4-dinitrophenylhydrazine (2,4-DNP), potentiated the antiproliferative and apoptotic effects of DHEA. We also determined whether decrease in nucleic acid synthesis (due to glucose-6-phosphate dehydrogenase inhibition by DHEA) contributes to DHEA-induced antiproliferation and apoptosis. Using a mixture of deoxyribonucleotides (DN) and ribonucleotides (RN), we showed that DNRN had little or no effect on DHEA-induced growth inhibition and apoptosis. We also showed that mevalonic acid (MVA) did not affect DHEA-induced antiproliferation and apoptotic effects, indicating that protein isoprenylation and membrane association are not affected by DHEA in BV-2 cells. Taken together, the present results demonstrate that depletion of ATP by DHEA plays an important role in DHEA-induced antiproliferation and apoptosis of BV-2 cells. (C) 2002 Elsevier Science Inc. All rights reserved.
ISSN: 0024-3205
DOI: 10.1016/s0024-3205(01)01542-9
Appears in Collections:食品暨應用生物科技學系

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