Inhibition of protein glycosylation and selective cytotoxicity toward virally transformed fibroblasts caused by B3-tunicamycin.
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| Abstract |
The biological effect of B3-tunicamycin, the only known homologue of tunicamycin which contains a saturated fatty-acid side chain, was examined using chick embryo fibroblasts, a mouse fibroblastic line (3T3) and a virally transformed mouse fibroblastic line (SV40-3T3). This homologue inhibited the transfer of N-acetylglucosamine 1-phosphate from UDP-N-acetylglucosamine to dolichyl phosphate, catalyzed by microsomes from chick liver or from cultured mouse fibroblasts. B3-tunicamycin also inhibited the incorporation of mannose into glycoproteins synthesized by chick or mouse fibroblasts. Incorporation of the amino acids proline and tyrosine was inhibited by B3-tunicamycin to a lesser extent than the incorporation of mannose. The mannose incorporation into glycoproteins synthesized by virally transformed cells was inhibited by B3-tunicamycin to a higher degree than what was achieved in the nontransformed lines or in the chick primary fibroblasts. When the activity of B3-tunicamycin as an inhibitor of protein glycosylation was compared to other homologues of tunicamycin, it was found to be the most active. This homologue caused complete (more than 95%) inhibition of protein glycosylation at a concentration of 50 ng/ml in chick and in mouse fibroblasts and at a concentration of 10 ng/ml in transformed mouse fibroblasts. When the cytotoxic activities of tunicamycin homologues were examined on nontransformed and virally transformed 3T3 cells, it was found that B3-tunicamycin displayed the highest selective cytotoxicity toward the transformed cells. When transformed fibroblasts (10(5) cells/plate) were treated with B3-tunicamycin (100 ng/ml) for 48 h, complete cell death was observed. The viability and the proliferative activity of the nontransformed fibroblast were normal even when treated with concentrations up to 500 ng/ml of B3-tunicamycin. This suggests that B3-tunicamycin may be a suitable candidate for studies of tumor growth in animals.
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| Authors | D Duksin, M Seiberg, W C Mahoney |
| Journal | European journal of biochemistry (Eur J Biochem) Vol. 129 Issue 1 Pg. 77-80 (Dec 1982) ISSN: 0014-2956 [Print] England |
| PMID | 7160386 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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