1. ¹Department of Lymphoma/Myeloma, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
2. ²Department of Clinical Immunology and AIDS Research Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
3. ³Department of Molecular Therapeutics, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

Correspondence: Dr NH Dang, MD Anderson Cancer Center, BOX 429, 1515 Holcombe Boulevard, Houston, TX 77030, USA. E-mail: nhdang@mail.mdanderson.org

⁴Contributed equally to this work.

Received 28 March 2003; Revised 15 July 2003; Accepted 15 July 2003.

Abstract

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.