Sorbitol-induced apoptosis of human leukemia is mediated by caspase activation and cytochrome c release.
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-X(L). 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.
Department of Experimental Medicine and Biochemical Sciences, University of Rome "Tor Vergata", Via Montpellier 1, 00133 Rome, Italy. gabriellamarfe@libero.it
Gabriella
G
Marfè
Emanuela
E
Morgante
Carla
C
Di Stefano
Livia
L
Di Renzo
Luisa
L
De Martino
Giuseppe
G
Iovane
Matteo Antonio
MA
Russo
Paola
P
Sinibaldi-Salimei
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis*; D045304:Cytochromes c / Q000096:biosynthesis*; D004247:DNA / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013012:Sorbitol / Q000494:pharmacology*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D013012:Sorbitol; D045304:Cytochromes c; D004247:DNA; D053148:Caspase 3