title: Combined treatment with fenretinide and indomethacin induces AIF-mediated, non-classical cell death in human acute T-cell leukemia Jurkat cells.
abstract: Currently used cytotoxic drugs in cancer therapy have a similar mechanism of action and low specificity. Applied simultaneously, they show an additive effect with strong side effects. Clinical trials with the use of different agents in cancer therapy show that the use of these compounds alone is not very effective in fighting cancer. An alternative solution could be to apply a combination of these agents, because their combination has a synergistic effect on some cancer cells. Therefore, in our investigations we examined the effects of a synthetic retinoid-fenretinide when combined with a non-steroidal anti-inflammatory drug-indomethacin on the process of apoptosis in the acute human T-cell leukemia cell line Jurkat. We demonstrate that treatment with the combination of the tested compounds induces the death of cells, that is peculiar and combines features of apoptosis as well as non-apoptotic cell death. In detail we observed, cell membrane permeabilization, phosphatydylserine exposure, no oligonucleosomal DNA fragmentation, no caspase-3 activation, but apoptosis inducing factor (AIF) nuclear translocation. Taken together these results indicate, that Jurkat cells after treatment with a combination of fenretinide and indomethacin undergo AIF-mediated programmed cell death.
authors.affiliation: Laboratory of Tumor Molecular Immunobiology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland. hojka@immuno.iitd.pan.wroc.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Hojka-Osinska
authors.forename: Ewa
authors.initials: E
authors.lastname: Ziolo
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rapak
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D017313:Fenretinide / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000378:metabolism*
chemical_list: C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D017313:Fenretinide; D007213:Indomethacin