creators_name: Gahlot, Satindra
creators_name: Khan, Mohammad Aslam
creators_name: Rishi, Loveena
creators_name: Majumdar, Sekhar
type: article
datestamp: 2011-12-08 18:58:40
lastmod: 2011-12-08 18:58:40
metadata_visibility: show
title: Pentoxifylline augments TRAIL/Apo2L mediated apoptosis in cutaneous T cell lymphoma (HuT-78 and MyLa) by modulating the expression of antiapoptotic proteins and death receptors.
ispublished: pub
subjects: QD
full_text_status: none
keywords:  Apoptosis; Cutaneous T cell lymphoma; Pentoxifylline; Tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand
note: Copyright of this article belongs to Elsevier Science
abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a promising anticancer agent but cutaneous T lymphoma cells (CTCL) are less sensitive to TRAIL-induced apoptosis. Here, we report that pentoxifylline (PTX), a phosphodiesterase inhibitor, augments TRAIL-mediated apoptosis in HuT-78 and MyLa cells through modulating extrinsic death receptors and intrinsic mitochondria dependent pathways. Our results clearly show that PTX augments TRAIL-mediated activation of caspase-8 and induces cleavage of Bid, although PTX alone cannot activate caspase-8. This is followed by cytochrome c release and subsequent, activation of caspase-9 and caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). Combined treatment downregulates the expression of various antiapoptotic proteins including c-FLIP, Bcl-xl, cIAP-1, cIAP-2 and XIAP. PTX induces the expression of death receptors DR4 and DR5 on cell surface of both the cell types where c-Jun NH2-terminal kinase (JNK) pathway plays an important role. Moreover, combined silencing of DR4 and DR5 by small interfering RNA abrogates the ability of PTX to induce TRAIL-mediated apoptosis. Thus, this is the first demonstration that PTX can potentiate TRAIL-mediated apoptosis through downregulation of cell survival gene products and upregulation of death receptors.
date: 2010-12-01
date_type: published
publication: Biochemical pharmacology
volume: 80
number: 11
publisher: Elsevier Science
pagerange: 1650-61
refereed: TRUE
issn: 1873-2968
official_url: http://www.sciencedirect.com/science/article/pii/S0006295210006271
related_url_url: http://www.sciencedirect.com/science/article/pii/S0006295210006271
related_url_type: pub
citation:   Gahlot, Satindra and Khan, Mohammad Aslam and Rishi, Loveena and Majumdar, Sekhar  (2010) Pentoxifylline augments TRAIL/Apo2L mediated apoptosis in cutaneous T cell lymphoma (HuT-78 and MyLa) by modulating the expression of antiapoptotic proteins and death receptors.  Biochemical pharmacology, 80 (11).  pp. 1650-61.  ISSN 1873-2968