Abstract
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.
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The present study focused on K562 cells, a bcr-abl-exspressing human chronic myelogenous leukemia line that has been reported to resistent induction of apoptosis by many of same stimuli. Sorbitol can induce apoptosis in cultured cells: (1) apoptosis is induced simply by the addition of the reagent to the culture medium and following withdrawal from the medium, (2) apoptotic response is quick and efficient.
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Marfè, G., Morgante, E., Di Stefano, C. et al. Sorbitol-induced apoptosis of human leukemia is mediated by caspase activation and cytochrome c release. Arch Toxicol 82, 371–377 (2008). https://doi.org/10.1007/s00204-007-0261-y
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DOI: https://doi.org/10.1007/s00204-007-0261-y