CD26/dipeptidyl peptidase IV enhances expression of topoisomerase II alpha and sensitivity to apoptosis induced by topoisomerase II inhibitors.
CD26/dipeptidyl peptidase IV (DPPIV) is a cell surface-bound ectopeptidase with important roles in T-cell activation and tumour biology. We now report that CD26/DPPIV enhances sensitivity to apoptosis induced by the antineoplastic agents doxorubicin and etoposide. In particular, CD26/DPPIV presence is associated with increased susceptibility to the mitochondrial pathway of apoptosis, documented by enhanced cleavage of poly (ADP ribose) polymerase (PARP), caspase-3 and caspase-9, Bcl-xl, and Apaf-1, as well as increased expression of death receptor 5 (DR5). We also show that the caspase-9-specific inhibitor z-LEHD-fmk inhibits drug-mediated apoptosis, leading to decreased PARP and caspase-3 cleavage, and reduced DR5 expression. Importantly, through detailed studies that demonstrate the association between topoisomerase II alpha expression and DPPIV activity, our data provide further evidence of the key role played by CD26 in biological processes.
Sato
K
K
Department of Lymphoma/Myeloma, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Aytac
U
U
Yamochi
T
T
Yamochi
T
T
Ohnuma
K
K
McKee
K S
KS
Morimoto
C
C
Dang
N H
NH
D017304:Annexin A5 / Q000378:metabolism; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053477:Apoptotic Protease-Activating Factor 1; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins; D018819:Dipeptidyl Peptidase 4 / Q000502:physiology*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011419:Propidium / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D059005:Topoisomerase II Inhibitors; D014162:Transfection; D051020:bcl-X Protein
C506592:APAF1 protein, human; D017304:Annexin A5; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D053477:Apoptotic Protease-Activating Factor 1; C494811:BCL2L1 protein, human; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C505639:TNFRSF10B protein, human; D059005:Topoisomerase II Inhibitors; D051020:bcl-X Protein; D011419:Propidium; D005047:Etoposide; D004317:Doxorubicin; D011065:Poly(ADP-ribose) Polymerases; D018819:Dipeptidyl Peptidase 4; D020169:Caspases; D004250:DNA Topoisomerases, Type II