UVA-activated 8-methoxypsoralen (PUVA) causes G2/M cell cycle arrest in Karpas 299 T-lymphoma cells.
We investigated the effect of UVA-activated 8-methoxypsoralen (PUVA) on the cell line Karpas 299 derived from anaplastic large-cell lymphoma (ALCL) expressing chimeric fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM/ALK). NPM/ALK activates phosphatidylinositol 3 kinase (PI3K)/Akt pathway responsible for the cell protection from apoptosis. We found that PUVA treatment first induced G2/M cell cycle arrest resulting in a decrease in the cell proliferation rate. The mitochondrial apoptosis was triggered immediately following PUVA treatment, as we judged from the unmasking of mitochondrial membrane antigen 7A6. However, the mitochondrial membrane depolarization was not observed and caspase-3 was only slightly activated. The late apoptotic events were lacking: neither translocation of phosphatidylserine to the outer side of plasma membrane nor DNA fragmentation occurred. We revealed that PUVA enhanced the expression of peroxiredoxin, stress protein endoplasmin and galectin-3. Galectin-3 has been shown to protect mitochondrial membrane integrity and prevent cytochrome c release thereby blocking the effector stage of apoptosis. We suggest that the elevated level of this protein following PUVA treatment acts in synergy with the constitutively expressed chimeric kinase NPM/ALK to block the apoptosis.
Bartosová
Jitka
J
Department of Cellular Biochemistry, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic. jitka.bartosova@uhkt.cz
Kuzelová
Katerina
K
Pluskalová
Michaela
M
Marinov
Iuri
I
Halada
Petr
P
Gasová
Zdenka
Z
D000077548:Anaplastic Lymphoma Kinase; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects*; D037502:Galectin 3 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008730:Methoxsalen / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D011701:PUVA Therapy / Q000009:adverse effects*; D010544:Peroxidases / Q000378:metabolism; D054464:Peroxiredoxins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D014466:Ultraviolet Rays
D018797:Cell Cycle Proteins; D037502:Galectin 3; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C102086:antigen 7A6; C053387:endoplasmin; D045304:Cytochromes c; D010544:Peroxidases; D054464:Peroxiredoxins; D019869:Phosphatidylinositol 3-Kinases; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D053148:Caspase 3; D008730:Methoxsalen