Effects of a novel antitumor depsipeptide, FR901228, on human breast cancer cells

Breast Cancer Res Treat. 1998 Sep;51(1):29-38. doi: 10.1023/a:1006091014092.

Abstract

Human breast cancer MCF7 and MDA-MB231 cells were used to investigate the biological and molecular activities of a novel naturally occurring agent, FR901228 (FR), that possesses a potent antitumor activity against human and murine tumor cells. Investigation of the cytotoxicity of FR and induction of internucleosomal DNA degradation in FR-treated cultures revealed that FR induced apoptotic-like cell death of MCF7 and MDA-MB231 cells. In FR-treated apoptotic cultures, flow cytometry revealed that there was a significant decrease of cells in S phase of the cell cycle. In FR-treated cells there was an increased expression of p21Cip1 and phosphorylation of Bcl-2 as determined by Western immunoblotting, and a novel cytoplasmic kinase of 33 kDa, p33 kinase, as determined by the in-gel kinase assay using myelin basic protein (MBP) as a substrate. Increased expression of p21CiP1, phosphorylation of Bcl-2, and activation of p33 MBP kinase may play part of the key mechanism for FR-induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Antibiotics, Antineoplastic / pharmacology*
  • Antibiotics, Antineoplastic / therapeutic use
  • Apoptosis
  • Blotting, Western
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis
  • Cyclins / genetics
  • DNA, Neoplasm / metabolism
  • Depsipeptides*
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Induction / drug effects
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Peptides, Cyclic*
  • Phosphorylation
  • Protein Kinases / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured / drug effects

Substances

  • Anti-Bacterial Agents
  • Antibiotics, Antineoplastic
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA, Neoplasm
  • Depsipeptides
  • Peptides, Cyclic
  • Proto-Oncogene Proteins c-bcl-2
  • romidepsin
  • Protein Kinases