Effects of human breast stromal cells on conjugated linoleic acid (CLA) modulated vascular endothelial growth factor-A (VEGF-A) expression in MCF-7 cells.
BACKGROUND
Conjugated linoleic acid (CLA), a naturally occurring compound found in ruminant dairy and beef products, has been shown to possess anti-cancer ability in vivo and in vitro. There are several CLA isomers in ruminant-produced food products, among which t10,c12-CLA and c9,t11-CLA are most potent. Vascular endothelial growth factor-A (VEGF-A) has been implicated as an angiogenesis-activating cytokine. Our previous results indicated that CLA induced suppression of VEGF-A in MCF-7 cells, which may be one of CLA's anticancer mechanisms.


METHODS
The effects of 10,c12-CLA and c9,t11-CLA on VEGF-A mRNA and protein expression in MCF-7 cells, which were co-cultured with human breast stromal cells isolated from breast tissues of surgical specimens of mammoplasty and breast cancer patients, were detected by RT-PCR and Western blot analysis.


RESULTS
VEGF-A mRNA and protein expressions were significantly (p < 0.05) elevated in co-cultured MCF-7 cells in comparison with cultured MCF-7 cells alone. Normal human breast stromal cells contribute greater effects in increasing VEGF-A protein expression in MCF-7 cells. Both t10,c12-CLA and c9,t11-CLA significantly (p < 0.05) decreased VEGF-A mRNA and protein levels in co-cultured MCF-7 cells. t10,c12-CLA appeared to be the more active isomer than c9, t11-CLA.


CONCLUSIONS
The results indicate that dietary CLA might serve as a chemo-therapeutic agent in human breast cancers by down-regulating VEGF-A expression.
Wang
Li-Shu
LS
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Huang
Yi-Wen
YW
Sugimoto
Yasuro
Y
Liu
Suling
S
Chang
Hsiang-Lin
HL
Ye
Weiping
W
Shu
Sherry
S
Lin
Young C
YC
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D015536:Down-Regulation; D006801:Humans; D007536:Isomerism; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
D014408:Biomarkers, Tumor; D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid