TY - JOUR
T1 - Sorbitol-induced apoptosis of human leukemia is mediated by caspase activation and cytochrome c release
AU - Marfè, Gabriella
AU - Morgante, Emanuela
AU - Di Stefano, Carla
AU - Di Renzo, Livia
AU - De Martino, Luisa
AU - Iovane, Giuseppe
AU - Russo, Matteo Antonio
AU - Sinibaldi-Salimei, Paola
PY - 2008/6
Y1 - 2008/6
N2 - It has been reported that sorbitol induces apoptosis in several cancer cell lines. However, the molecular mechanism underlying the sorbitol-induced apoptotic process is not yet clearly understood. In the present study, the intracellular signaling pathways of sorbitol-induced apoptosis in human K562 cells were investigated using both morphological analysis and DNA fragmentation technique. In this study, we demonstrated that sorbitol-induced apoptosis in human K562 cells is a concentration- and time-dependent manner. This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax, and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-XL. Moreover, the sorbitol treatment resulted in a significant reduction of mitochondria membrane potential, increase in the release of mitochondrial cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by sorbitol involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all participate in sorbitol-induced apoptotic process in human K562 cells.
AB - It has been reported that sorbitol induces apoptosis in several cancer cell lines. However, the molecular mechanism underlying the sorbitol-induced apoptotic process is not yet clearly understood. In the present study, the intracellular signaling pathways of sorbitol-induced apoptosis in human K562 cells were investigated using both morphological analysis and DNA fragmentation technique. In this study, we demonstrated that sorbitol-induced apoptosis in human K562 cells is a concentration- and time-dependent manner. This sorbitol-induced apoptosis in human K562 cells was also accompanied by the up-regulation of Bax, and down-regulation of p-Bcl-2, but no effect on the levels of Bcl-XL. Moreover, the sorbitol treatment resulted in a significant reduction of mitochondria membrane potential, increase in the release of mitochondrial cytochrome c (cyt c), and activation of caspase 3. Furthermore, treatment with caspase 3 inhibitor (z-DEVD-fmk) was capable of preventing the sorbitol-induced caspase 3 activity and cell death. These results clearly demonstrate that the induction of apoptosis by sorbitol involves multiple cellular/molecular pathways and strongly suggest that pro- and anti-apoptotic Bcl-2 family proteins, mitochondrial membrane potential, mitochondrial cyt c, and caspase 3, they all participate in sorbitol-induced apoptotic process in human K562 cells.
KW - Apoptosis
KW - Bcl-2
KW - Bcl-xL
KW - Caspases
KW - Sorbitol
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U2 - 10.1007/s00204-007-0261-y
DO - 10.1007/s00204-007-0261-y
M3 - Article
C2 - 18046541
AN - SCOPUS:44449157283
VL - 82
SP - 371
EP - 377
JO - Archiv fur Toxikologie
JF - Archiv fur Toxikologie
SN - 0003-9446
IS - 6
ER -