Soyasaponin-I-modified invasive behavior of cancer by changing cell surface sialic acids

Objective. Sialylation involving tumor formation and invasive behavior goes along with altered sialyltransferase (ST) activity. A potent ST inhibitor, soyasaponin I (Ssal), was discovered to selectively inhibit the cellular alpha2.3-sialyltranserase activity In this study, we further test the effects of Ssal on modifing the metastatic and invasive behaviors of cancer cell lines. Methods. Nonmetastatic breast cancer cell line, MCF-7, and highly metastastic breast cancer cell line, MDA-MB-231, were used to investigate the effects of Ssal oil tumor cells. Results. Ssal did not affect cell growth cycle and also failed to inhibit cell growth in this study (the concentration of Ssal less than or equal to100 muM). Ssal was as predicted to successfully inhibit cellular alpha2,3-ST activity and depressed the dose-dependent tumor cell surface alpha2.3-sialic acid expression. In addition, different concentrations of Ssal did stimulate MCF-7 cell adhesion to collagen tape I linearly and significantly enhanced cell adhesion to the Matrigel-matrix. Furthermore, Ssal significantly decreased MDA-MB-231 cell migration. Reverse transcriptase polymerase chain reaction for evaluating mRNA expression of ST3Gal I,III and IV showed that Ssal also down-regulated the expression of ST3Gal IV but did not affect the other two. Conclusions. The results showed that Ssal was implicated in the invasive behavior of tumor cells, suggesting that altered alpha2,3-sialylation pathway played a crucial role in the adhesion and tumor metastases. Ssal is a good candidate for studying the biological roles of ST. and might provide a new preventive strategy in tumor metastasis. (C) 2004 Elsevier Inc. All rights reserved.