Anti-leukemic activities of Dictyostelium secondary metabolites:: A novel aromatic metabolite, 4-methyl-5-n-pentylbenzene-1,3-diol, isolated from Dictyostelium mucoroides suppresses cell growth in human leukemia K562 and HL-60 cells
Anti-leukemic activities of Dictyostelium secondary metabolites:: A novel aromatic metabolite, 4-methyl-5-n-pentylbenzene-1,3-diol, isolated from Dictyostelium mucoroides suppresses cell growth in human leukemia K562 and HL-60 cells
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DOI：
10.1016/j.lfs.2006.08.034
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发表时间：
2006-12-14
期刊：
影响因子：
6.1
通讯作者：
Kubohara, Yuzuru
中科院分区：
文献类型：
--
作者：
Kikuchi, Haruhisa;Oshima, Yoshiteru;Kubohara, Yuzuru
先前的研究表明，DIF-1是细胞黏菌盘状盘孢霉的一种分化诱导因子，在哺乳动物肿瘤细胞中具有抗肿瘤活性，并且可以用盘状盘孢霉中的氨基糖类似物呋喃葡萄糖胺（FDs）或二糖氨基葡萄糖胺（dg）、n-乙酰氨基葡萄糖胺衍生物（D. purpureum中的DG-A和D.盘状盘孢霉中的DG-B）诱导PC12细胞的神经元分化。因此，细胞黏菌是一种有吸引力的天然资源，可以提供有价值的先导化合物，用于药理学和医学领域。在这项研究中，我们从细胞黏菌D. mucoroides的子实体中分离出一种新的芳香化合物，4-甲基-5-n-戊基苯-1,3-二醇（MPBD），并评估了MPBD、FDs和DGs对人白血病K562和HL-60细胞的体外抗增殖活性。MPBD在20-80 μ M剂量依赖性地抑制K562和HL-60细胞的生长。10 ~ 80 μ M的FDs对细胞生长无影响，10 ~ 40 μ M的DGs对细胞生长有剂量依赖性抑制。虽然我们没有发现FDs和DGs在原始生物中的作用，但我们发现5-20 μ M的MPBD促进了盘状天牛茎细胞的形成。本研究结果表明MPBD、DGs及其衍生物在治疗癌症方面具有潜在的治疗潜力，并证实了我们对细胞黏菌作为药物资源的期望。(c) 2006爱思唯尔公司版权所有。
It has previously been shown that DIF-1, a differentiation-inducing factor of the cellular slime mold Dictyostelium discoideum, possesses antitumor activities in mammalian tumor cells and that neuronal differentiation of PC12 cells can be induced with furanodictines (FDs), aminosugar analogs found in D. discoideum, or dictyoglucosamines (DGs), N-acetyl glucosamine derivatives (DG-A from D. purpureum and DG-B from D. discoideum). Thus, cellular slime molds are attractive natural resources that may provide valuable lead compounds to be utilized in the field of pharmacology and medicine. In this study, we have isolated a novel aromatic compound, 4-methyl-5-n-pentylbenzene-1,3-diol (MPBD), from fruiting bodies of the cellular slime mold D. mucoroides and assessed the in vitro antiproliferative activities of MPBD, FDs, and DGs in human leukemia K562 and HL-60 cells. MPBD at 20-80 mu M dose-dependently suppressed cell growth in both K562 and HL-60 cells. While FDs at 10-80 mu M did not affect cell growth, DGs at 10-40 mu M dose-dependently suppressed cell growth in the cells. Although we failed to find the roles of FDs and DGs in the original organisms, MPBD at 5-20 mu M was found to promote stalk cell formation in D. discoideum. The present results indicate that MPBD, DGs or their derivatives may have therapeutic potential in the treatment of cancer and confirm our expectations regarding cellular slime molds as drug resources. (c) 2006 Elsevier Inc. All rights reserved.