AAF-cmk sensitizes tumor cells to trail-mediated apoptosis.
TRAIL is a member of the tumor necrosis factor (TNF) superfamily. This cytokine is cytotoxic for a high proportion of tumor cells, but could be also toxic for normal cells. There is a need to find other agents able to potentiate the antitumor effects of this cytokine. In our study, we found that Ala-Ala-Phe-chloromethylketone (AAF-cmk) augmented cytotoxic activity of TRAIL or TNF against human leukemic cells. Flow cytometry studies and electron microscopy revealed that apoptosis was primarily responsible for this potentiation. Altogether, our studies indicate that AAF-cmk might effectively sensitize human leukemia cells to apoptosis induced by TRAIL and TNF.
Młnarczuk
Izabela
I
Department of Immunology, Center of Biostructure, The Medical University of Warsaw, Chalubińskiego 5, 02004 Warsaw, Poland.
Mróz
Paweł
P
Hoser
Grazyna
G
Nowis
Dominika
D
Biały
Łukasz P
ŁP
Ziemba
Halina
H
Grzela
Tomasz
T
Feleszko
Wojciech
W
Malejczyk
Jacek
J
Wójcik
Cezary
C
Jakóbisiak
Marek
M
Gołab
Jakub
J
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C055604:alanyl-alanyl-phenylalanine chloromethyl ketone; D011065:Poly(ADP-ribose) Polymerases