title: Sorbitol induces apoptosis of human colorectal cancer cells via p38 MAPK signal transduction.
abstract: Sorbitol has been reported to have anticancer effects in several tumor models, however its effects on colorectal cancer remain elusive. In the present study, the effects of sorbitol on growth inhibition and apoptosis in the colorectal cancer HCT116 cell line were evaluated and its mechanism of action was examined. An MTT assay was utilized to determine the effect of sorbitol on HCT116 cell proliferation at different time points and variable doses. Western blot analysis was used to examine the effect of sorbitol on apoptosis-related protein expression and the p38 MAPK signaling pathway. The results revealed that sorbitol may inhibit the growth of HCT116 cells in a time- and dose-dependent manner. Following treatment with sorbitol for 3 h, western blotting demonstrated cleavage of the caspase-3 zymogen protein and a cleavage product of poly (ADP-ribose) polymerase (PARP), a known substrate of caspase-3, was also evident. During sorbitol-induced apoptosis, the mitochondrial pathway was activated by a dose-dependent increase in Bax expression and cytochromecrelease, while the expression of anti-apoptotic protein Bcl-2 was significantly decreased in a dose-dependent manner. The investigation for the downstream signal pathway revealed that sorbitol-induced apoptosis was mediated by an increase in phosphorylated p38 MAPK expression. Overall, the observations from the present study imply that sorbitol causes increased levels of Bax in response to p38 MAPK signaling, which results in the initiation of the mitochondrial death cascade. Therefore, sorbitol is a promising candidate as a potential chemotherapeutic agent for the treatment of colorectal cancer HCT116 cells.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, P.R. China ; Department of Pathology, Junan Hospital, Changchun, Jilin, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P.R. China.
authors.forename: Yong-Kun
authors.initials: YK
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Beihua University, Jilin, P.R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Gai
keywords: apoptosis; colorectal cancer; mitochondrial death cascade; p38 mitogen-activated protein kinases; sorbitol