OBJECTIVE: 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 alpha2,3-sialyltranserase activity. In this study, we further test the effects of SsaI on modifying 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 SsaI on tumor cells. RESULTS: SsaI did not affect cell growth cycle and also failed to inhibit cell growth in this study (the concentration of SsaI < or=100 muM). SsaI 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 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. CONCLUSIONS: The results showed that SsaI 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. SsaI is a good candidate for studying the biological roles of ST, and might provide a new preventive strategy in tumor metastasis.
OBJECTIVE: 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 alpha2,3-sialyltranserase activity. In this study, we further test the effects of SsaI on modifying 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 SsaI on tumor cells. RESULTS:SsaI did not affect cell growth cycle and also failed to inhibit cell growth in this study (the concentration of SsaI < or=100 muM). SsaI 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 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. CONCLUSIONS: The results showed that SsaI 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. SsaI is a good candidate for studying the biological roles of ST, and might provide a new preventive strategy in tumor metastasis.
Authors: Adam E Sienkiewicz; Brandon N Rosenberg; Genea Edwards; Teresia A Carreon; Sanjoy K Bhattacharya Journal: Proteomics Clin Appl Date: 2014-03-07 Impact factor: 3.494
Authors: Aurélie Cazet; Sylvain Julien; Marie Bobowski; Joy Burchell; Philippe Delannoy Journal: Breast Cancer Res Date: 2010-06-08 Impact factor: 6.466
Authors: Marta Pérez-Garay; Beatriz Arteta; Lluís Pagès; Rafael de Llorens; Carme de Bolòs; Fernando Vidal-Vanaclocha; Rosa Peracaula Journal: PLoS One Date: 2010-09-01 Impact factor: 3.240