Induction of apoptosis in Jurkat cells by photoexcited psoralen derivatives: Implication of mitochondrial dysfunctions and caspases activation.
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.
Viola
G
G
Department of Pharmaceutical Sciences, University of Padova, Italy. giampietro.viola.1@unipd.it
Fortunato
E
E
Cecconet
L
L
Disarò
S
S
Basso
G
G
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D011564:Furocoumarins / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008730:Methoxsalen / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D011564:Furocoumarins; D017382:Reactive Oxygen Species; C011659:angelicin; D020169:Caspases; D008730:Methoxsalen