Assistant Professor, Chung-Ang University, Department of Food and Nutrition, 72-1 Nae-ri, Daedeok-myeon, Anseong-si, Gyeonggi-do, 456-756, South Korea.
Anticancer Res. 2010 Jul;30(7):2881-4.
Complex dietary sphingolipids such as sphingomyelin and glycosphingolipids have been reported to inhibit the development of colon cancer. This protective role may be the result of the conversion of complex sphingolipids to bioactive metabolites including sphingoid bases (sphingosine and sphinganine) and ceramide, which inhibit proliferation and stimulate apoptosis. In the current study, we evaluated the significance of the 4,5-trans double bond by comparing the effects of sphingosine and the cell permeable short-chain ceramide analog C(2)-ceramide to those of sphinganine and C(2)-dihydroceramide, which lack this structural feature. The effects of the sphingoid bases, C(2)-ceramide, and C(2)-dihydroceramide on apoptosis were determined by detecting 200-bp DNA ladders or hypo-diploid areas (sub-G(0)/G(1)), indicative of apoptosis, in HCT-116 human colon cancer cells. In addition, the effects of the sphingoid bases at an apoptotic concentration for 12 hours on cell cycle distribution were determined by flow cytometry. The results indicated that the sphingoid bases and C(2)-ceramide induced apoptosis, whereas C(2)-dihydroceramide had no effects. Sphingoid bases arrested the cell cycle at the G(2)/M phase. The present study provides evidence that the 4,5-trans double bond is necessary for the apoptotic effect of C(2)-ceramide, but not for that of sphingoid bases.
复杂的膳食神经鞘脂，如神经鞘磷脂和糖鞘脂，已被报道能抑制结肠癌的发展。这种保护作用可能是由于复杂神经鞘脂转化为生物活性代谢物，包括神经酰胺、神经酰胺和神经酰胺，从而抑制增殖和刺激细胞凋亡。在本研究中，我们通过比较鞘氨醇和细胞通透的短链神经酰胺类似物 C(2)-神经酰胺与缺乏这种结构特征的神经氨醇和 C(2)-二氢神经酰胺的作用，评估了 4,5-反式双键的意义。通过检测 200-bp DNA 梯或低二倍体区（亚 G(0)/G(1)），即凋亡的指示，来确定鞘氨醇、C(2)-神经酰胺和 C(2)-二氢神经酰胺对 HCT-116 人结肠癌细胞凋亡的影响。此外，通过流式细胞术确定了鞘氨醇在凋亡浓度下 12 小时对细胞周期分布的影响。结果表明，鞘氨醇和 C(2)-神经酰胺诱导细胞凋亡，而 C(2)-二氢神经酰胺则没有作用。鞘氨醇将细胞周期阻滞在 G(2)/M 期。本研究提供的证据表明，4,5-反式双键是 C(2)-神经酰胺凋亡作用所必需的，但不是鞘氨醇所必需的。
