Apoptotic Effects of N-(2-Hydroxyphenyl)-2-Propylpentanamide on U87-MG and U-2 OS Cells and Antiangiogenic Properties

Anticancer Agents Med Chem. 2021;21(11):1451-1459. doi: 10.2174/1871520620666200728125356.

Abstract

Background and objective: 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.

Materials and methods: 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.

Results: HO-AAVPA had antiproliferative effects at 48h with an IC50=0.655mM in U87-MG cells and an IC50=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.

Conclusion: HO-AAVPA has antiproliferative effects on glioblastoma and osteosarcoma and antiangiogenic properties.

Keywords: Antiproliferative; HO-AAVPA; U-2 OS.; U87-MG; antiangiogenic properties; proapoptotic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / antagonists & inhibitors
  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / chemistry
  • Angiogenesis Inhibitors / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Neovascularization, Pathologic / chemically induced
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Pentanes / antagonists & inhibitors
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Amides
  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • N-(2-hydroxyphenyl)-2-propylpentanamide
  • Pentanes