Honokiol is a FOXM1 antagonist.
Honokiol is a FOXM1 antagonist.
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DOI：
10.1038/s41419-017-0156-7
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发表时间：
2018-01-24
影响因子：
9
通讯作者：
Gartel AL
中科院分区：
文献类型：
--
作者：
Halasi M;Hitchinson B;Shah BN;Váraljai R;Khan I;Benevolenskaya EV;Gaponenko V;Arbiser JL;Gartel AL
和厚朴是一种天然产物，也是一种新兴药物，用于治疗各种恶性肿瘤，包括造血系统恶性肿瘤、肉瘤和常见的上皮肿瘤。honoklastine对多种具有不同遗传背景的恶性肿瘤的广泛活性表明honoklastine抑制多种恶性肿瘤共同的活性。致癌转录因子FOXM1是人类癌症中最高表达的癌蛋白之一。在这里，我们发现，和厚朴酚抑制FOXM1介导的转录和FOXM1蛋白的表达。更重要的是，我们发现和诺啡肽对FOXM1的抑制作用是和诺啡肽与FOXM1结合的结果。这种结合是特定的honoklane，二聚烯丙基苯酚，并没有观察到的化合物，无论是单体烯丙基苯酚或未取代的二羟基苯酚。这表明烯丙基酚的取代和二聚化都是与FOXM1物理相互作用所必需的。因此，我们证明了一种新的和特定的机制，FOXM1抑制honokaline，这部分可以解释其在癌细胞中的抗癌活性。
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.
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影响因子：
23.9
作者：
Saito Y;Chapple RH;Lin A;Kitano A;Nakada D
通讯作者：
Nakada D
影响因子：
--
作者：
Avtanski DB;Nagalingam A;Bonner MY;Arbiser JL;Saxena NK;Sharma D
通讯作者：
Sharma D
DOI：
10.1158/1078-0432.ccr-08-0102
发表时间：
2008-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Garcia A;Zheng Y;Zhao C;Toschi A;Fan J;Shraibman N;Brown HA;Bar-Sagi D;Foster DA;Arbiser JL
通讯作者：
Arbiser JL
影响因子：
20.3
作者：
Ishitsuka, K;Hideshima, T;Anderson, KC
通讯作者：
Anderson, KC
影响因子：
6.5
作者：
Funa, Nina S.;Reddy, Kalpana;Arbiser, Jack L.
通讯作者：
Arbiser, Jack L.