Takahashi N, Iwahori A, Breitman T R, Fukui T
Department of Health Chemistry, Hoshi University, Tokyo, Japan.
Oncol Res. 1997;9(10):527-33.
All-trans-Retinoic acid (RA) induces differentiation and inhibits growth of many tumor types. Whereas the RA nuclear receptors mediate genomic effects of RA, there also are many nongenomic effects that do not have defined mechanisms. Some nongenomic effects of RA may involve retinoylation (RA acylation), a posttranslational modification of proteins occurring in many eukaryotic cell lines including the human breast cancer cell line MCF-7. To gain further knowledge of the role(s) of retinoylation, we studied the effects of tunicamycin (TM), an inhibitor of both protein N-glycosylation and palmitoylation, on growth and retinoylation in MCF-7 cells. We found that RA or TM alone inhibited growth of MCF-7 cells. Combinations of RA and TM inhibited growth synergistically. TM increased retinoylation and decreased palmitoylation. These results suggest that increased retinoylation and decreased glycosylation and palmitoylation may play a role in the synergistic inhibition of cell growth by combinations of TM and RA in MCF-7 cells. Furthermore, our results suggest that combinations of TM and RA may have clinical utility.
全反式维甲酸（RA）可诱导多种肿瘤类型的分化并抑制其生长。虽然RA核受体介导RA的基因组效应，但也存在许多机制尚不明确的非基因组效应。RA的一些非基因组效应可能涉及视黄酰化（RA酰化），这是一种发生在包括人乳腺癌细胞系MCF-7在内的许多真核细胞系中的蛋白质翻译后修饰。为了进一步了解视黄酰化的作用，我们研究了衣霉素（TM）（一种蛋白质N-糖基化和棕榈酰化的抑制剂）对MCF-7细胞生长和视黄酰化的影响。我们发现单独使用RA或TM均可抑制MCF-7细胞的生长。RA与TM联合使用可协同抑制细胞生长。TM可增加视黄酰化并减少棕榈酰化。这些结果表明，视黄酰化增加以及糖基化和棕榈酰化减少可能在TM与RA联合使用对MCF-7细胞生长的协同抑制中发挥作用。此外，我们的结果表明TM与RA联合使用可能具有临床应用价值。
