Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan, ROC.
Prostaglandins Other Lipid Mediat. 2011 Apr;94(3-4):104-11. doi: 10.1016/j.prostaglandins.2011.01.004. Epub 2011 Mar 17.
Cyclopentenone prostaglandin 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)), which is generated from the dehydration of PGD(2), is a natural ligand of peroxisome proliferator-activated receptor gamma (PPARγ) and a potential apoptotic mediator. The synthetic PPARγ ligands, troglitazone and ciglitazone, inhibit tumor progression in many cells by PPARγ activation, but the mechanism of 15d-PGJ(2) is still unclear. In this study, GW9662, an antagonist of PPARγ, and quercetin, a natural antioxidant, were used to study the apoptotic mechanism of 15d-PGJ(2) in A549 cells. Results showed that 15d-PGJ(2) induced apoptosis, which was associated with the production of reactive oxygen species (ROS) and the decrease of GSH levels. Furthermore, quercetin reduced the activity of caspases in 15d-PGJ(2)-induced apoptotic processes. These results suggest that 15d-PGJ(2) induces apoptosis in A549 cells mainly through the formation of ROS; it does not depend on PPARγ activation. Moreover, these findings support the use of quercetin and PPARγ agonists in non-small cell lung carcinoma.
环戊烯酮前列腺素 15-去二氢-Δ(12,14)-前列腺素 J(2)(15d-PGJ(2))，由 PGD(2)脱水生成，是过氧化物酶体增殖物激活受体γ(PPARγ)的天然配体，也是一种潜在的凋亡介质。合成的 PPARγ 配体曲格列酮和西格列酮通过 PPARγ 激活抑制许多细胞中的肿瘤进展，但 15d-PGJ(2)的机制尚不清楚。在这项研究中，使用 PPARγ 拮抗剂 GW9662 和天然抗氧化剂槲皮素研究 15d-PGJ(2)在 A549 细胞中的凋亡机制。结果表明，15d-PGJ(2)诱导的凋亡与活性氧(ROS)的产生和 GSH 水平的降低有关。此外，槲皮素降低了 15d-PGJ(2)诱导的凋亡过程中半胱天冬酶的活性。这些结果表明，15d-PGJ(2)主要通过形成 ROS 诱导 A549 细胞凋亡，不依赖于 PPARγ 激活。此外，这些发现支持使用槲皮素和 PPARγ 激动剂治疗非小细胞肺癌。
