Induction of apoptosis by (-)-gossypol-enriched cottonseed oil in human breast cancer cells.
Induction of apoptosis is one of the mechanisms of chemotherapeutic agents against breast cancer. In addition, recent studies have shown that diets containing polyphenolic components possess anticancer activities either in vitro or in vivo by inhibiting cell proliferation and inducing apoptosis. The aim of our study was to explore the effects of (-)-gossypol-enriched cottonseed oil [(-)-GPCSO], a polyphenolic compound, on the proliferation of the breast cancer cell line MCF-7 as well as primary cultured human breast cancer epithelial cells (PCHBCEC). We investigated whether the mechanism of the effects of (-)-GPCSO was mediated via the induction of cell apoptosis and the regulation of Bcl-2 gene expression at both the mRNA and protein levels. Our results showed that (-)-GPCSO inhibited the proliferation of MCF-7 and PCHBCEC in a dose-dependent manner. (-)-GPCSO (0.1 and 0.2%) induced DNA fragmentation in both MCF-7 cells and PCHBCEC. (-)-GPCSO suppressed the expression of Bcl-2 at both the mRNA and protein levels in MCF-7 cells and PCHBCEC in a dose-dependent fashion. Our results suggest that the growth inhibitory effect of (-)-GPCSO on MCF-7 and PCHBCEC is due, at least partially, to the induction of cell apoptosis, which is mediated by down-regulation of Bcl-2 expression at both the mRNA and protein levels. It might be possible for (-)-GPCSO to be developed as a novel chemotherapeutic agent for breast cancer patients.
Ye
Weiping
W
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Chang
Hsiang-Lin
HL
Wang
Li-Shu
LS
Huang
Yi-Wen
YW
Shu
Sherry
S
Sugimoto
Yasuro
Y
Dowd
Michael K
MK
Wan
Peter J
PJ
Lin
Young C
YC
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003369:Cottonseed Oil / Q000737:chemistry / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006072:Gossypol / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003369:Cottonseed Oil; D019253:Proto-Oncogene Proteins c-bcl-2; D006072:Gossypol