Pentoxifylline induces apoptosis in vitro in cutaneous T cell lymphoma (HuT-78) and enhances FasL mediated killing by upregulating Fas expression.
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.
Rishi
Loveena
L
Division of Cell Biology and Immunology, Institute of Microbial Technology (CSIR), Chandigarh 160036, India.
Gahlot
Satindra
S
Kathania
Mahesh
M
Majumdar
Sekhar
S
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010431:Pentoxifylline / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
C491901:FAS protein, human; D053222:Fas Ligand Protein; D019014:fas Receptor; D010431:Pentoxifylline