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 (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.
Hsu
Chi-Cheng
CC
Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan.
Lin
Tzu-Wen
TW
Chang
Wei-Wei
WW
Wu
Chi-Yue
CY
Lo
Wan-Hsia
WH
Wang
Peng-Hui
PH
Tsai
Ying-Chieh
YC
D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D004791:Enzyme Inhibitors; D012503:Saponins; D012794:Sialic Acids; C056684:soyasaponin I; D009828:Oleanolic Acid; D012799:Sialyltransferases; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase; C000722087:ST3GAL1 protein, human