Effects of hibarimicins and hibarimicin-related compounds produced by Microbispora on v-Src kinase activity and growth and differentiation of human myeloid leukemia HL-60 cells.
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| Abstract |
We studied the effects of hibarimicins and hibarimicin-related compounds produced by Microbispora rosea subsp. hibaria [glycosides (hibarimicins A, B, C, D, E, G, H and I) and aglycon (hibarimicinone)] or compounds produced by its mutants [glycosides (HMP-P4 and -Y6), aglycons (HMP-P1 and -Y1) and shunt products (HMP-M1, M2, M3 and -M4)] on v-Src tyrosine kinase and growth and differentiation of human myeloid leukemia HL-60 cells. Among them, hibarimicin B was a strong and the most selective v-Src kinase inhibitor with differentiation inducing activity of HL-60 cells. Hibarimicin E similarly induced HL-60 cell differentiation but had no v-Src kinase inhibitory activity. Hibarimicinone was the most potent v-Src kinase inhibitor, although less selective, and did not induce differentiation of HL-60 cells. Hibarimicin B competitively inhibited ATP binding to the v-Src kinase, but hibarimicinone showed noncompetitive inhibition. These two compounds, however, showed similar mixed types of inhibition against a Src substrate binding to the v-Src kinase. Altogether, these results suggest that signaling molecules other than Src might be more important in the differentiation induction of HL-60 cells.
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| Authors | Sung Ig Cho, Hidesuke Fukazawa, Yoshio Honma, Takayuki Kajiura, Hiroshi Hori, Yasuhiro Igarashi, Tamotsu Furumai, Toshikazu Oki, Yoshimasa Uehara |
| Journal | The Journal of antibiotics (J Antibiot (Tokyo)) Vol. 55 Issue 3 Pg. 270-8 (Mar 2002) ISSN: 0021-8820 [Print] England |
| PMID | 12014442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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