Resorcylic acid lactone L-783,277 inhibits the growth of the human adrenal cancer cell line H295R in vitro

Int J Immunopathol Pharmacol. Oct-Dec 2009;22(4):889-95. doi: 10.1177/039463200902200404.

Abstract

The resorcylic acid lactone L-783,277, isolated from a Phoma sp. (ATCC 74403), is a potent and specific inhibitor of MEK (Map kinase kinase) that exerts very interesting pharmacological activities including anti-neoplastic properties. However, the role of this compound in the regulation of endocrine-related cancer cell growth and tumor progression remains unknown. In the present study we have evaluated the effect of L-783,277 on the viability, proliferation and cell cycle of the human adrenocortical carcinoma cell line H295R. L-783,277 inhibited viability (IC50 of 22 microM) and cell proliferation (IC50 of 21 microM) of H295R. At concentrations of 10(-6)-10(-8)M this effect was associated with the accumulation of H295R cells in S-phase, whereas at concentrations of 10(-9)-10(-10)M a prolonged G1-phase and reduced transition into S-phase were observed. Our findings demonstrate for the first time the anti-proliferative action of L-783,277 on the human adrenocortical H295R cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / enzymology
  • Adrenal Cortex Neoplasms / pathology*
  • Adrenocortical Carcinoma / enzymology
  • Adrenocortical Carcinoma / pathology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Inhibitory Concentration 50
  • Lactones / pharmacology*
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Resorcinols / pharmacology*

Substances

  • Antineoplastic Agents
  • L 783277
  • Lactones
  • Protein Kinase Inhibitors
  • Resorcinols
  • Mitogen-Activated Protein Kinase Kinases