Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells

Br J Cancer. 1997;76(1):21-8. doi: 10.1038/bjc.1997.330.

Abstract

The antiproliferative effects of gossypol on human MCF-7 mammary cancer cells and cyclin D1-transfected HT-1060 human fibrosarcoma cells were investigated by cell cycle analysis and effects on the cell cycle regulatory proteins Rb and cyclin D1. Flow cytometry of MCF-7 cells at 24 h indicated that 10 microM gossypol inhibited DNA synthesis by producing a G1/S block. Western blot analysis using anti-human Rb antibodies and anti-human cyclin D1 antibodies in MCF-7 cells and high- and low-expression cyclin D1-transfected fibrosarcoma cells indicated that, after 6 h exposure, gossypol decreased the expression levels of these proteins in a dose-dependent manner. Gossypol also decreased the ratio of phosphorylated to unphosphorylated Rb protein in human mammary cancer and fibrosarcoma cell lines. Gossypol (10 microM) treated also decreased cyclin D1-associated kinase activity on histone H1 used as a substrate in MCF-7 cells. These results suggest that gossypol might suppress growth by modulating the expression of cell cycle regulatory proteins Rb and cyclin D1 and the phosphorylation of Rb protein.

Publication types

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

MeSH terms

  • Breast Neoplasms / pathology*
  • Cell Cycle / drug effects
  • Cyclin D1
  • Cyclins / antagonists & inhibitors*
  • Cyclins / genetics
  • Fibrosarcoma / genetics
  • Fibrosarcoma / pathology*
  • Gossypol / pharmacology*
  • Humans
  • Mitosis / drug effects
  • Oncogene Proteins / antagonists & inhibitors*
  • Oncogene Proteins / genetics
  • Retinoblastoma Protein / antagonists & inhibitors*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Cyclins
  • Oncogene Proteins
  • Retinoblastoma Protein
  • Cyclin D1
  • Gossypol