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

• Published in: Gynecologic oncology Vol. 96; no. 2; pp. 415 - 422
• Main Authors: Hsu, Chi-Cheng, Lin, Tzu-Wen, Chang, Wei-Wei, Wu, Chi-Yue, Lo, Wan-Hsia, Wang, Peng-Hui, Tsai, Ying-Chieh
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2005
• Subjects: Adhesion; Breast Neoplasms - enzymology; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cell Adhesion - drug effects; Cell Cycle - drug effects; Cell Line, Tumor - drug effects; Cell Movement - drug effects; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Extracellular Matrix - pathology; Humans; Migration; Neoplasm Invasiveness; Neoplasm Metastasis; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - pharmacology; Saponins - pharmacology; Sialic acid; Sialic Acids - metabolism; Sialyltransferase; Sialyltransferase inhibitor; Sialyltransferases - antagonists & inhibitors; Sialyltransferases - metabolism; Soyasaponin I; Sialic acid; Migration; Sialyltransferase inhibitor; Soyasaponin I; Sialyltransferase; Adhesion; Cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2004.10.010

Sialylation involving tumor formation and invasive behavior goes along with altered sialyltransferase (ST) activity. A potent ST inhibitor, soyasaponin I (SsaI), was discovered to selectively inhibit the cellular α2,3-sialyltranserase activity. In this study, we further test the effects of SsaI on modifying the metastatic and invasive behaviors of cancer cell lines.
Nonmetastatic breast cancer cell line, MCF-7, and highly metastastic breast cancer cell line, MDA-MB-231, were used to investigate the effects of SsaI on tumor cells.
SsaI did not affect cell growth cycle and also failed to inhibit cell growth in this study (the concentration of SsaI ≤100 μM). SsaI was as predicted to successfully inhibit cellular α2,3-ST activity and depressed the dose-dependent tumor cell surface α2,3-sialic acid expression. In addition, different concentrations of SsaI did stimulate MCF-7 cell adhesion to collagen type I linearly and significantly enhanced cell adhesion to the Matrigel-matrix. Furthermore, SsaI significantly decreased MDA-MB-231 cell migration. Reverse transcriptase polymerase chain reaction for evaluating mRNA expression of ST3Gal I, III and IV showed that SsaI also down-regulated the expression of ST3Gal IV but did not affect the other two.
The results showed that SsaI was implicated in the invasive behavior of tumor cells, suggesting that altered α2,3-sialylation pathway played a crucial role in the adhesion and tumor metastases. SsaI is a good candidate for studying the biological roles of ST, and might provide a new preventive strategy in tumor metastasis.