Conjugated linoleic acid inhibits DNA synthesis and induces apoptosis in TSU-Pr1 human bladder cancer cells.
BACKGROUND
Conjugated linoleic acid (CLA) has strong chemoprotective properties in experimental animal models. The insulin-like growth factor (IGF) system has been implicated as a risk factor for the development of bladder cancer. The present study examined CLA regulation of TSU-Pr1 bladder cancer cell proliferation and apoptosis and the influence of CLA on IGF-I receptor (IGF-IR) signaling.


METHODS
TSU-Pr1 cells were cultured in serum-free medium with 0, 2, 5, or 10 microM CLA and/or 10 nM IGF-I. [3H]Thymidne incorporation, DNA laddering, FACS analysis, immunoprecipitation and Western blotting were performed.


RESULTS
CLA decreased DNA synthesis and induced apoptosis in TSU-Pr1 cells dose-dependently. Exogenous IGF-I alone increased viable cell numbers but did not counteract growth inhibition induced by CLA. CLA decreased IGF-IR and insulin receptor substrate (IRS)-1 protein levels. In addition, CLA decreased IGF-I-induced phosphorylation of IGF-IR and IRS-1, recruitment of the p85 subunit of phosphoinositide 3-kinase to IRS-1 and phosphorylation of Akt and extracellular signal-regulated kinase-1/2.


CONCLUSIONS
These results suggest that CLA inhibits cell proliferation and stimulates apoptosis of TSU-Pr1 cells via its inhibition of the IGF-IR signaling pathway.
Oh
Yoon S
YS
Division of Life Sciences, Hallym University, 1 Okchon Dong, Chunchon, 200-702, Korea.
Lee
Hyun S
HS
Cho
Han J
HJ
Lee
Sang G
SG
Jung
Kyeong C
KC
Park
Jung H
JH
D017209:Apoptosis / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004261:DNA Replication / Q000187:drug effects / Q000235:genetics; D004273:DNA, Neoplasm / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms
D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm; D044243:Linoleic Acids, Conjugated; D012333:RNA, Messenger; D013936:Thymidine