α-linolenic acid inhibits human renal cell carcinoma cell proliferation through PPAR-γ activation and COX-2 inhibition.
ω-3 fatty acids have potential anticancer effects, and consuming food rich in ω-3 fatty acids reduces the human renal cell carcinoma (RCC) risk. However, the direct effect of ω-3 fatty acids on RCCin vitrois unknown. In the present study, the effects of α-linolenic acid (ALA), an ω-3 fatty acid, were observed on cell proliferation in the RCC cell line OS-RC-2. The activity and gene expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ) and cyclooxygenase-2 (COX-2) in the OS-RC-2 cells were measured by ELISA and real-time RT-PCR, respectively, following ALA treatment. ALA (20-80μM) dose-dependently suppressed the proliferation of the OS-RC-2 cells. PPAR-γ activity and gene expression were significantly increased by ALA at 20 and 40μM. COX-2 activity and gene expression levels were significantly decreased by ALA from 20μM. Use of purely the PPAR-γ agonist, rosiglitazone, decreased the proliferation of the OS-RC-2 cells, while ALA induced further suppression of cell proliferation in the presence of rosiglitazone. The COX-2 inhibitor N-(3-Pyridyl)indomethacinamide induced further suppression of cell proliferation in the presence of rosiglitazone. N-(3-Pyridyl)indomethacinamide also suppressed the proliferation of the OS-RC-2 cells. In the presence of N-(3-Pyridyl)indomethacinamide, ALA and rosiglitazone further inhibited OS-RC-2 cell proliferation. In conclusion, ALA inhibits the cell proliferation of the OS-RC-2 human RCC cell line. PPAR-γ activation and COX-2 inhibition serve as two signaling pathways for the inhibitory effects of ALA on RCC cell proliferation.
Departments of Urology, Fourth Military Medical University, Xi'an, Shaanxi, P.R. China ;
Lijun
L
Yang
Jianlin
J
Yuan
Liwen
L
Liu
Changhong
C
Shi
Longxin
L
Wang
Feng
F
Tian
Fei
F
Liu
He
H
Wang
Chen
C
Shao
Qiang
Q
Zhang
Zhinan
Z
Chen
Weijun
W
Qin
Weihong
W
Wen
cell proliferation; cyclooxygenase-2; peroxisome proliferator-activated receptor-γ; renal cell carcinoma; α-linolenic acid