Effects of serum on (-)-gossypol-suppressed growth in human prostate cancer cells.

Abstract

BACKGROUND:

Gossypol, a natural polyphenolic compound present in cottonseeds, possesses antiproliferative and pro-apoptotic effects in in vivo and in vitro models. There are two enantiomers, (+)-gossypol and (-)-gossypol, the latter being a more potent inhibitor of cancer cell growth. Here, the effect of bovine serum albumin (BSA) and dextran-coated charcoal-treated fetal bovine serum (DCC-FBS)-containing medium on the ability of (-)-gossypol to inhibit the growth of human prostate cancer cells was studied.

MATERIALS AND METHODS:

BSA- and DCC-FBS-supplemented medium were used to examine the influence of serum proteins on the antiproliferative effects of (-)-gossypol in DU-145 cells, a human prostate cancer cell line. The viability of the DU-145 cells was determined by CellTiter 96 Aqueous assay. The expressions of mRNA and protein for the cell cycle regulators, cyclin-D1, Rb, CDK, p21 and TGF-beta, were determined by RT-PCR and Western blot analyses, respectively.

RESULTS:

(-)-Gossypol caused growth suppression of the DU-145 cells. In comparison with BSA-supplemented medium, DCC-FBS blocked the antiproliferative effects of (-)-gossypol at 1 and 2.5 microM, but not at 5 microM. Furthermore, (-)-gossypol treatment down-regulated cyclin-D1, Rb, CDK4 and CDK6, and up-regulated p21 and TGF-beta1 at the mRNA and/or protein levels.

CONCLUSION:

The data suggested that (-)-gossypol-suppressed prostate cancer cell growth may be influenced through cell cycle regulators, which may lead to better prognosis. We further speculate that (-)-gossypol might serve as a chemotherapeutic agent for human prostate cancer patients.

• Authors: Yi-Wen Huang, Li-Shu Wang, Hsiang-Lin Chang, Weiping Ye, Yasuro Sugimoto, Michael K Dowd, Peter J Wan, Young C Lin
• Journal: Anticancer research (Anticancer Res) 2006 Sep-Oct Vol. 26 Issue 5A Pg. 3613-20 ISSN: 0250-7005 [Print] Greece
• PMID: 17094491 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• Dextrans
• RNA, Messenger
• RNA, Neoplasm
• Retinoblastoma Protein
• Transforming Growth Factor beta1
• Cyclin D1
• Charcoal
• Serum Albumin, Bovine
• CDK4 protein, human
• CDK6 protein, human
• Cyclin-Dependent Kinase 4
• Cyclin-Dependent Kinase 6
• Gossypol

Topics

• Animals
• Blotting, Western
• Cattle
• Cell Survival (drug effects)
• Charcoal (chemistry)
• Cyclin D1 (genetics, metabolism)
• Cyclin-Dependent Kinase 4 (genetics, metabolism)
• Cyclin-Dependent Kinase 6 (genetics, metabolism)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics, metabolism)
• Dextrans (chemistry)
• Gossypol (pharmacology)
• Humans
• Male
• Neoplasms, Hormone-Dependent (metabolism, pathology)
• Prostatic Neoplasms (metabolism, pathology)
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Retinoblastoma Protein (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Serum (chemistry, metabolism)
• Serum Albumin, Bovine (pharmacology)
• Transforming Growth Factor beta1 (genetics, metabolism)
• Tumor Cells, Cultured