Department of Food Science and Biotechnology, National Chung Hsing University, Taichung 402, Taiwan ROC.
J Nutr Biochem. 2012 Sep;23(9):1155-62. doi: 10.1016/j.jnutbio.2011.06.009. Epub 2011 Dec 1.
In our previous study, we demonstrated that lycopene can inhibit the proliferation of androgen-dependent prostate LNCaP cancer cells through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ)-liver X receptor alpha (LXRα)-ATP-binding cassette transporter 1 (ABCA1) pathway. However, it is still unclear whether lycopene possesses similar effects in androgen-independent prostate cancer cells DU145 and PC-3. As lycopene inhibited the proliferation of both cell types to a similar extent, we chose DU145 cells for most of the subsequent studies. We show that lycopene significantly increased protein and mRNA expression of PPARγ, LXRα and ABCA1 and cholesterol efflux (i.e., decreased cellular cholesterol and increased cholesterol in culture medium). Lycopene (10 μM) in the presence of a specific antagonist of PPARγ (GW9662) or of LXRα (GGPP) restored the proliferation of DU145 cells and significantly suppressed lycopene-induced protein and mRNA expression of PPARγ and LXRα and cholesterol efflux. Liver X receptor α knockdown by siRNA against LXRα significantly promoted the proliferation of DU145 cells, whereas si-LXRα knockdown followed by incubation with lycopene (10 μM) restored the proliferation to the control level. Furthermore, lycopene in combination with the LXRα agonist T0901317 exhibited synergistic effects on cell proliferation and protein expression of PPARγ, LXRα and ABCA1. These results demonstrate that lycopene can inhibit DU145 cell proliferation via PPARγ-LXRα-ABCA1 pathway and that lycopene and T0901317 exhibit synergistic effects.
在我们之前的研究中，我们证明了番茄红素可以通过激活过氧化物酶体增殖物激活受体γ（PPARγ）-肝 X 受体α（LXRα）-ATP 结合盒转运蛋白 1（ABCA1）途径来抑制雄激素依赖性前列腺 LNCaP 癌细胞的增殖。然而，番茄红素是否对雄激素非依赖性前列腺癌细胞 DU145 和 PC-3 具有类似的作用仍不清楚。由于番茄红素对这两种细胞类型的增殖都有相似的抑制作用，我们选择 DU145 细胞进行了大部分后续研究。我们发现番茄红素显著增加了 PPARγ、LXRα 和 ABCA1 的蛋白和 mRNA 表达，以及胆固醇外流（即减少细胞内胆固醇并增加培养基中的胆固醇）。在存在 PPARγ 特异性拮抗剂（GW9662）或 LXRα 特异性拮抗剂（GGPP）的情况下，番茄红素（10 μM）恢复了 DU145 细胞的增殖，并显著抑制了番茄红素诱导的 PPARγ 和 LXRα 的蛋白和 mRNA 表达以及胆固醇外流。用 LXRα 的 siRNA 敲低 LXRα 显著促进了 DU145 细胞的增殖，而 si-LXRα 敲低后用番茄红素（10 μM）孵育可使增殖恢复至对照水平。此外，番茄红素与 LXRα 激动剂 T0901317 联合使用对细胞增殖和 PPARγ、LXRα 和 ABCA1 的蛋白表达表现出协同作用。这些结果表明，番茄红素可以通过 PPARγ-LXRα-ABCA1 途径抑制 DU145 细胞的增殖，并且番茄红素和 T0901317 表现出协同作用。
