Moschetta A, Portincasa P, van Erpecum K J, Debellis L, Vanberge-Henegouwen G P, Palasciano G
Department of Internal and Public Medicine, Section of Internal Medicine, University of Bari Medical School, Bari, Italy.
Dig Dis Sci. 2003 Jun;48(6):1094-101. doi: 10.1023/a:1023712712025.
High fecal deoxycholate levels may promote colonic cancer. Phospholipids protect against bile salt-induced cytotoxicity. We therefore aimed to examine whether the dietary phospholipid sphingomyelin could decrease hyperproliferation induced by deoxycholate. In CaCo2 cells, hyperproliferation (by bromodeoxyuridine assay), phosphorylation state of cellular proteins, and apoptosis with concomitant caspase-3 activity were evaluated after incubation with 50-500 microM deoxycholate, with or without sphingomyelin. At 2 and 4 hr of incubation, deoxycholate induced dose-dependent apoptosis, with concomitant caspase-3 activation. At 16 hr, apoptosis had decreased markedly, but there was dose-dependent hyperproliferation (with changed phosphorylation status of cellular proteins) at this time point. Sphingomyelin dose-dependently reduced deoxycholate-induced apoptosis and hyperproliferation. In conclusion, sphingomyelin reduces deoxycholate-induced hyperproliferation and apoptosis. These findings may have implications for colonic cancer prevention by dietary modification.
高粪便脱氧胆酸盐水平可能会促进结肠癌。磷脂可抵御胆盐诱导的细胞毒性。因此，我们旨在研究膳食磷脂鞘磷脂是否能减少脱氧胆酸盐诱导的过度增殖。在用50 - 500微摩尔脱氧胆酸盐孵育CaCo2细胞时，无论有无鞘磷脂，均评估其过度增殖（通过溴脱氧尿苷测定）、细胞蛋白的磷酸化状态以及伴随半胱天冬酶 - 3活性的凋亡情况。孵育2小时和4小时时，脱氧胆酸盐诱导剂量依赖性凋亡，并伴随半胱天冬酶 - 3激活。孵育16小时时，凋亡明显减少，但此时存在剂量依赖性过度增殖（细胞蛋白磷酸化状态改变）。鞘磷脂剂量依赖性地减少脱氧胆酸盐诱导的凋亡和过度增殖。总之，鞘磷脂可减少脱氧胆酸盐诱导的过度增殖和凋亡。这些发现可能对通过饮食调整预防结肠癌具有重要意义。
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