Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells.
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.
Ligueros
M
M
Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA.
Jeoung
D
D
Tang
B
B
Hochhauser
D
D
Reidenberg
M M
MM
Sonenberg
M
M
D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D019938:Cyclin D1; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000235:genetics; D005354:Fibrosarcoma / Q000235:genetics / Q000473:pathology*; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors*; D014162:Transfection; D014407:Tumor Cells, Cultured
D016213:Cyclins; D015513:Oncogene Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D006072:Gossypol