Viola G, Fortunato E, Cecconet L, Disarò S, Basso G
Department of Pharmaceutical Sciences, University of Padova, Italy.
Toxicol In Vitro. 2007 Mar;21(2):211-6. doi: 10.1016/j.tiv.2006.09.016. Epub 2006 Sep 30.
The prevailing form of cell death in lymphocytes exposed to psoralen plus UVA light (PUVA), was investigated. We studied the well known drug 8-methoxypsoralen (8-MOP) and an angular derivatives: angelicin (ANG). We evaluated the induction of apoptosis in a human tumor T-cell line (Jurkat). Both compounds provoke a significant induction of apoptosis at 24h from irradiation as demonstrated by a remarkable percentage of cells Annexin-V positive. We investigated the effects of the psoralen derivatives upon UVA irradiation on the cell cycle. The flow cytometric analysis of propidium labeled cells indicates that treatment induces, in a dose dependent manner, a massive accumulation of cells, for both compounds, in G2-S phase after 24h from the irradiation. We have focused our attention on the mitochondrial functionality after irradiation in the presence of psoralen derivatives. We evaluated, by flow cytometry, (i) the mitochondrial potential (Deltapsi(mt)), (ii) the production of reactive oxygen species (ROS) and (iii) the oxidation of cardiolipin, a phospholipid restricted to the inner mitochondrial membrane. Furthermore the activation of caspases -3, -8 and -9 was also investigated. The obtained data indicated that, upon UVA irradiation, the two compounds induce a strong decrease in mitochondrial functions and activate caspase-3, -8 and -9.
研究了暴露于补骨脂素加紫外线A光（PUVA）的淋巴细胞中主要的细胞死亡形式。我们研究了著名的药物8-甲氧基补骨脂素（8-MOP）和一种角形衍生物：当归素（ANG）。我们评估了在人肿瘤T细胞系（Jurkat）中凋亡的诱导情况。两种化合物在照射后24小时均引发了显著的凋亡诱导，Annexin-V阳性细胞的比例显著证明了这一点。我们研究了补骨脂素衍生物对UVA照射后细胞周期的影响。碘化丙啶标记细胞的流式细胞术分析表明，两种化合物处理后，在照射后24小时，以剂量依赖的方式诱导细胞在G2-S期大量积累。我们将注意力集中在补骨脂素衍生物存在下照射后的线粒体功能上。我们通过流式细胞术评估了（i）线粒体膜电位（ΔΨ(mt)），（ii）活性氧（ROS）的产生，以及（iii）心磷脂的氧化，心磷脂是一种局限于线粒体内膜的磷脂。此外，还研究了半胱天冬酶-3、-8和-9的激活情况。获得的数据表明，在UVA照射后，这两种化合物会导致线粒体功能大幅下降，并激活半胱天冬酶-3、-8和-9。
