Takahashi N, Iwahori A, Kawai K, Fukui T
Faculty of Pharmaceutical Sciences, Hoshi University, Shinagawa-ku, Tokyo, 142-8501, Japan.
Arch Biochem Biophys. 1998 Dec 1;360(1):113-20. doi: 10.1006/abbi.1998.0922.
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.
法尔考宁酮A和B是从子囊菌纲真菌法尔考埃默氏菌或小果埃默氏菌的菌丝体提取物中分离出的新型黄色色素，其结构与视黄酸（RA）相似。迄今为止，尚未报道法尔考宁酮的生物活性。在此，我们报道了法尔考宁酮A单独使用或与RA联合使用时可抑制HL60人白血病细胞的生长。法尔考宁酮A单独使用不会诱导HL60细胞分化。然而，法尔考宁酮A增强了10 nM RA诱导的HL60细胞分化，且其作用具有协同性。另一方面，法尔考宁酮A的4'-去甲基衍生物法尔考宁酮B在抑制细胞生长方面的活性远低于法尔考宁酮A。此外，法尔考宁酮A的合成衍生物法尔考宁酮A对溴苯腙和法尔考宁酮A二肟在抑制细胞生长和诱导分化方面比天然的法尔考宁酮A和B更有效。这些化合物诱导HL60细胞分化为单核细胞/巨噬细胞样细胞，不同于RA诱导的粒细胞样细胞。这些结果表明，法尔考宁酮A可能是一种新型抗增殖剂，且法尔考宁酮A环戊烯酮环4'位的甲基残基可能对其生物活性是必需的。此外，法尔考宁酮A增强了RA诱导的HL60细胞分化，而其衍生物单独显示出对HL60细胞的生长抑制和分化诱导作用。基于这些结果，法尔考宁酮A及其衍生物在白血病治疗中可能具有临床应用价值。
