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  • Title: Induction of differentiation in human promyelocytic leukemia cell line HL60 by a new type of polyenes, falconensone A and its derivatives.
    Author: Takahashi N, Iwahori A, Kawai K, Fukui T.
    Journal: Arch Biochem Biophys; 1998 Dec 01; 360(1):113-20. PubMed ID: 9826436.
    Abstract:
    Falconensones A and B are new type of yellow pigment isolated from the mycelial extract of ascomycetous fungi, Emericella falconensis or Emericella fruticulosa, whose structures are similar to retinoic acid (RA). To date, biological activities of falconensones have not been reported. Herein, we reported that falconensone A inhibited growth of HL60 human leukemia cells, when used either singly or in combination with RA. Falconensone A alone did not induce differentiation of HL60 cells. However, falconesone A enhanced the differentiation of HL60 cells induced by 10 nM RA, and its effect was synergistic. On the other hand, falconensone B, the 4'-nor-methyl derivative of falconensone A, showed much lower activity than falconensone A on the inhibition of cell growth. In addition, synthetic derivatives of falconensone A, falconensone A p-bromophenylhydrazone and falconensone A dioxime, were more potent on the inhibition of cell growth and the induction of differentiation than natural falconensones A and B. These compounds induced differentiation of HL60 cells into monocyte/macrophage-like cells, different from granulocyte-like cells induced by RA. These results suggest that falconensone A may be a new type of antiproliferative agent, and that the methyl residue at the 4' position of the cyclopentenone ring of falconensone A may be necessary for biological activity. In addition, falconensone A enhanced RA-induced differentiation of HL60 cells, while its derivatives alone showed growth inhibition and induction of differentiation of HL60 cells. Based on these results, falconensone A and its derivatives may have clinical utility in the treatment of leukemia.
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