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

Rishi, Loveena and Gahlot, Satindra and Kathania, Mahesh and Majumdar, Sekhar (2009) Pentoxifylline induces apoptosis in vitro in cutaneous T cell lymphoma (HuT-78) and enhances FasL mediated killing by upregulating Fas expression. Biochemical pharmacology, 77 (1). pp. 30-45. ISSN 1873-2968

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Abstract

Constitutive nuclear factor-kappaB (NF-kappaB) 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-kappaB. Apoptosis was ascertained by sub-G1 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-kappaB 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.

Item Type:	Article
Additional Information:	Copyright of this article belongs to Elsevier Science
Uncontrolled Keywords:	Cutaneous T cell lymphoma; Pentoxifylline; Apoptosis; Fas; ROI
Subjects:	Q Science > QD Chemistry
Depositing User:	Dr. K.P.S.Sengar
Date Deposited:	08 Dec 2011 19:37
Last Modified:	08 Dec 2011 19:37
URI:	http://crdd.osdd.net/open/id/eprint/579

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