Department of Medicine, University of Illinois, Chicago, IL, USA.
Department of Biochemistry and Molecular Genetics, University of Illinois, Chicago, IL, USA.
Cell Death Dis. 2018 Jan 24;9(2):84. doi: 10.1038/s41419-017-0156-7.
Honokiol is a natural product and an emerging drug for a wide variety of malignancies, including hematopoietic malignancies, sarcomas, and common epithelial tumors. The broad range of activity of honokiol against numerous malignancies with diverse genetic backgrounds suggests that honokiol is inhibiting an activity that is common to multiple malignancies. Oncogenic transcription factor FOXM1 is one of the most overexpressed oncoproteins in human cancer. Here we found that honokiol inhibits FOXM1-mediated transcription and FOXM1 protein expression. More importantly, we found that honokiol's inhibitory effect on FOXM1 is a result of binding of honokiol to FOXM1. This binding is specific to honokiol, a dimerized allylphenol, and was not observed in compounds that either were monomeric allylphenols or un-substituted dihydroxy phenols. This indicates that both substitution and dimerization of allylphenols are required for physical interaction with FOXM1. We thus demonstrate a novel and specific mechanism for FOXM1 inhibition by honokiol, which partially may explain its anticancer activity in cancer cells.
和厚朴酚是一种天然产物，也是一种新兴的药物，可用于多种恶性肿瘤，包括血液系统恶性肿瘤、肉瘤和常见的上皮肿瘤。和厚朴酚对多种具有不同遗传背景的恶性肿瘤具有广泛的活性，这表明和厚朴酚抑制了多种恶性肿瘤共有的一种活性。致癌转录因子 FOXM1 是人类癌症中过度表达的癌蛋白之一。在这里，我们发现和厚朴酚抑制 FOXM1 介导的转录和 FOXM1 蛋白表达。更重要的是，我们发现和厚朴酚对 FOXM1 的抑制作用是和厚朴酚与 FOXM1 结合的结果。这种结合是和厚朴酚特有的，它是一种二聚化的烯丙基酚，而在单体烯丙基酚或未取代的二羟基酚类化合物中则没有观察到。这表明烯丙基酚的取代和二聚化都需要与 FOXM1 发生物理相互作用。因此，我们证明了和厚朴酚抑制 FOXM1 的一种新的、特异性的机制，这可能部分解释了它在癌细胞中的抗癌活性。
