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1,8-二基-3-甲基-氨基因通过HIF-1α下调抑制瘤血管生成

Su Jung Hwang¹, Seung Hye Cho¹, Hye Jung Bang¹

¹School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Biochemical pharmacology

|December 10, 2023

概括

一种新型化合物,Photorhabdus luminescens中的1,8-dihydroxy-3-methoxyanthraquinone (DMA),通过向低氧诱导因子-1α (HIF-1α) 和相关途径而有效抑制瘤血管生成,而无毒性.

科学领域:

微生物学微生物学
自然产品化学自然产品化学
癌症生物学癌症生物学

背景情况:

Photorhabdus luminescens是一种生物发光细菌,在昆虫病原性线虫中发现.
从自然资源中寻找生物活性化合物的探索导致了光化合物的分离.
该化合物被确定为1,8-二基-3-甲基氨基 (DMA).

研究的目的:

研究DMA在抑制瘤血管生成方面的潜力.
评估DMA对缺氧诱导因子-1α (HIF-1α) 和其下游目标的影响.
评估DMA在体外和体内癌症模型中的安全性和有效性.

主要方法:

使用LC/MS,TLC,HR-ESI-MS和NMR从P. luminescens中分离和阐明DMA的结构.
在体外研究中使用人类结直肠癌HCT116细胞和人类带血管内皮细胞 (HUVEC).
使用斑马鱼胚胎进行体内研究,以评估抗血管性和毒理效应.

主要成果:

在没有细胞毒性的情况下,DMA抑制了HIF-1α蛋白稳定性和转录激活.
DMA抑制了VEGF介导的内皮细胞管的形成,迁移和入侵.
在斑马鱼胚胎中,DMA表现出抗血管性质,没有任何不良影响.
通过降低PI3K/AKT和c-RAF/ERK通路的调节,DMA抑制了瘤的生长.

结论:

DMA是瘤血管生成和HIF-1α的强有力的抑制剂.
作为癌症治疗的治疗候选者,DMA显示出希望.
DMA的机制包括准关键信号通路,如HIF-1α和PI3K/AKT/ERK.

关键词:

血管新生的产生.人类氨酸 (Anthraquinone) 是一种生物发光细菌的生物发光细菌这就是HIF-1α.一个叫Photorhabdus luminescensens的光源.在VEGF中,VEGF是VEGF.

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