Growth inhibition and mechanism of action of p-dodecylaminophenol against refractory human pancreatic cancer and cholangiocarcinoma

Bioorg Med Chem. 2012 Apr 15;20(8):2520-6. doi: 10.1016/j.bmc.2012.02.060. Epub 2012 Mar 7.

Abstract

Pancreatic cancer and cholangiocarcinoma are aggressive and drug-resistant refractory cancers. Based on N-(4-hydroxyphenyl)retinamide (3), a synthetic amide of all-trans-retinoic acid (RA), p-dodecylaminophenol (1) was developed to be an effective anticancer agent without key side-effects of these agents. Compound 1 suppresses cell growth of pancreatic cancer (MIA Paca2) and cholangiocarcinoma (HuCCT1), potentially by inhibiting ras expression and signaling through ERK pathways in MIA Paca2 cells and both ERK and Akt pathways in HuCCT1 cells. Compound 1 inhibits proliferation of these cells to a greater extent than either RA or 3. Compound 1 may represent a potent and useful anti-cancer drug for use against pancreatic cancer and cholangiocarcinoma that lacks their key side-effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminophenols / chemical synthesis
  • Aminophenols / chemistry
  • Aminophenols / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / pathology
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Aminophenols
  • Antineoplastic Agents