Curcumin selectively induces apoptosis in cutaneous T-cell lymphoma cell lines and patients' PBMCs: potential role for STAT-3 and NF-kappaB signaling.

Curcumin inhibits cell growth and induces apoptosis in a number of tumor cell lines and animal models. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 8 g per day. The purpose of this study was to address the antitumor effect of curcumin on cutaneous T-cell lymphoma (CTCL) cell lines and peripheral blood mononuclear cells (PBMCs) from patients with CTCL compared with healthy donors' controls. Curcumin at 5-20 microM for 24 and 48 hours induced apoptosis in a time- and dose-dependent manner in three CTCL cell lines (namely MJ, Hut78, and HH). Curcumin at 5-20 microM for 48 hours also caused more apoptosis in patients' PBMCs compared with healthy donors' PBMCs (P<0.05). Curcumin decreased protein and mRNA expression levels of signal transducer and activator of transcription (STAT)-3, bcl-2, and survivin in three cell lines and in patients' PBMCs. Curcumin inhibited STAT-3 and IkappaB-alpha phosphorylation, as well as suppressed DNA binding of nuclear factor (NF)-kappaB in these cells. Caspase-3 was activated and poly (ADP-Ribose) polymerase was cleaved after curcumin treatment. These data suggest that curcumin selectively induces apoptosis in association with the downregulation of STAT-3 and NF-kappaB signaling pathways in CTCL cells. Our findings provide a mechanistic rationale for the potential use of curcumin as a therapeutic agent for patients with CTCL.