Department of Microbiology, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Carpio y Plan de Ayala S/N, Casco de Santo Tomas, Mexico, CDMX. 11340, Mexico.
Subdireccion de Investigacion Basica, Intituto Nacional de Cancerologia, Ciudad de Mexico, Mexico.
Anticancer Agents Med Chem. 2021;21(11):1451-1459. doi: 10.2174/1871520620666200728125356.
Histone Deacetylases (HDACs) are important therapeutic targets for many types of human cancers. A derivative of valproic acid, N-(2-hydroxyphenyl)-2-propylpentanamide (HOAAVPA), has antiproliferative properties on some cancer cell lines and inhibits the HDAC1 isoform.
In this work, HO-AAVPA was tested as an antiproliferative agent in U87-MG (human glioblastoma) and U-2 OS cells (human osteosarcoma), which are types of cancer that are difficult to treat, and its antiangiogenic properties were explored.
HO-AAVPA had antiproliferative effects at 48h with an IC=0.655mM in U87-MG cells and an IC=0.453mM in U-2 OS cells. Additionally, in the colony formation assay, HO-AAVPA decreased the number of colonies by approximately 99% in both cell lines and induced apoptosis by 31.3% in the U-2 OS cell line and by 78.2% in the U87-MG cell line. Additionally, HO-AAVPA reduced the number of vessels in Chorioallantoic Membranes (CAMs) by approximately 67.74% and IL-6 levels in both cell lines suggesting that the biochemical mechanism on cancer cell of HO-AAVPA is different compared to VPA.
HO-AAVPA has antiproliferative effects on glioblastoma and osteosarcoma and antiangiogenic properties.
组蛋白去乙酰化酶（HDACs）是许多类型人类癌症的重要治疗靶点。丙戊酸的一种衍生物，N-（2-羟基苯基）-2-丙基戊酰胺（HOAAVPA），对一些癌细胞系具有抗增殖作用，并抑制 HDAC1 同工型。
在这项工作中，HO-AAVPA 被测试为 U87-MG（人胶质母细胞瘤）和 U-2 OS 细胞（人骨肉瘤）的增殖抑制剂，这两种癌症类型难以治疗，并探索了其抗血管生成特性。
HO-AAVPA 在 48 小时内对 U87-MG 细胞的 IC=0.655mM 和 U-2 OS 细胞的 IC=0.453mM 具有抗增殖作用。此外，在集落形成试验中，HO-AAVPA 在两种细胞系中使集落数量减少了约 99%，并在 U-2 OS 细胞系中诱导了 31.3%的细胞凋亡，在 U87-MG 细胞系中诱导了 78.2%的细胞凋亡。此外，HO-AAVPA 在鸡胚尿囊膜（CAM）中使血管数量减少了约 67.74%，并降低了两种细胞系中的 IL-6 水平，表明 HO-AAVPA 对癌细胞的生化机制与 VPA 不同。
HO-AAVPA 对胶质母细胞瘤和骨肉瘤具有抗增殖作用和抗血管生成特性。
