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.
Zhang
Chunlei
C
Department of Dermatology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. czhang@mdanderson.org
Li
Baoqiang
B
Zhang
Xiang
X
Hazarika
Parul
P
Aggarwal
Bharat B
BB
Duvic
Madeleine
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077022:Survivin; D000072000:NF-KappaB Inhibitor alpha; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D003474:Curcumin