Pentoxifylline induces apoptosis in vitro in cutaneous T cell lymphoma (HuT-78) and enhances FasL mediated killing by upregulating Fas expression

Constitutive nuclear factor-kappa B (NF-kappa B) is known to play an important role in the survival of HuT-78 cells, a cutaneous T cell lymphoma (CTCL) cell line. Here, we have demonstrated that pentoxifylline (PTX), a phosphodiesterase inhibitor, can trigger a series of events leading to apoptosis in HuT-78 cells without affecting NF-kappa B. Apoptosis was ascertained by sub-G(1) peak analysis and TUNEL assay. Apoptosis induced by PTX in HuT-78 cells involved mitochondrial hyperpolarization, cytochrome c release, caspase-3 activation and PARP cleavage. Further, it was found that PTX treatment downregulated Bcl-xl and c-FLIP expression without affecting constitutive NF-kappa B but upregulated activator protein-1 (AP-1). Low concentration of PTX upregulated Fas and TRAIL expression in HuT-78 cells. In addition, PTX can act as a scavenger of reactive oxygen intermediate and it could enhance FasL mediated killing in HuT-78 cells. Our results taken together indicated that PTX may be a potential agent for killing CTCL cells. (C) 2008 Elsevier Inc. All rights reserved