TY  - JOUR
ID  - open499
UR  - http://www.sciencedirect.com/science/article/pii/S0006295210006271
IS  - 11
A1  - Gahlot, Satindra
A1  - Khan, Mohammad Aslam
A1  - Rishi, Loveena
A1  - Majumdar, Sekhar
N2  - 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.
VL  - 80
TI  - 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.
AV  - none
EP  - 61
N1  - Copyright of this article belongs to Elsevier Science
Y1  - 2010/12/01/
PB  - Elsevier Science
JF  - Biochemical pharmacology
KW  -  Apoptosis; Cutaneous T cell lymphoma; Pentoxifylline; Tumor necrosis factor-related apoptosis-inducing ligand/Apo2 ligand
SN  - 1873-2968
SP  - 1650
ER  -