Differential Gene Expression in Rat Vascular Smooth Muscle Cells Following Treatment with Coptisine Exerts a Selective Antiproliferative Effect

作者：Suzuki Hiroka; Tanabe Hiroki; Mizukami Hajime; Inoue Makoto^*

来源：Journal of Natural Products, 2011, 74(4): 634-638.

DOI：10.1021/np100645d

It is known that coptisine (1), an isoquinoline alkaloid, selectively inhibits proliferation of rat primary vascular smooth muscle cells,(VSMCs). In the present study, the characteristics of its antiproliferative effect on several types of smooth muscle like cells were investigated and compared to the effects of berberine (2) and palmatine (3). TO Clarify further the mechanism underlying the VSMC-selective, antiproliferative effect of 1; the genes responsible were investigated by determining which mRNAs showed expression regulated by 1. Coptisine (1) showed greater antiproliferative effect on smooth muscle cells derived from the aorta than on those derived from other organs. Analysis of the MRNA expression revealed that 1 upregulated two genes, growth arrest and DNA-damage-inducible alpha (Gadd45a) and response: gene to Complement32 (Rgc32). Both genes remained unchanged in 3Y1 fibroblasts and were not affected by 2 and 3. Coptisine (l) was found to induce the mRNA of the Gadd45a and Rgc32 genes, Specifically in VSMC. Activation of these genes by 1 may Mediate inhibition of cell cycle progression. However, as these genes tare commonly expressed in various. Cell types, a selective target for 1 activity is likely to exist.; upstream;:of these genes..

• 出版日期2011-4