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Curcumin selectively induces apoptosis in cutaneous T-cell lymphoma cell lines and patients' PBMCs: potential role for STAT-3 and NF-kappaB signaling.
- Source :
-
The Journal of investigative dermatology [J Invest Dermatol] 2010 Aug; Vol. 130 (8), pp. 2110-9. Date of Electronic Publication: 2010 Apr 15. - Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- Apoptosis drug effects
Apoptosis physiology
Autophagy drug effects
Autophagy physiology
Caspase 3 metabolism
Cell Division drug effects
Cell Division physiology
Cell Line, Tumor
Humans
I-kappa B Proteins metabolism
Inhibitor of Apoptosis Proteins
Leukocytes, Mononuclear drug effects
Leukocytes, Mononuclear metabolism
Leukocytes, Mononuclear pathology
Lymphoma, T-Cell metabolism
Lymphoma, T-Cell pathology
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
NF-KappaB Inhibitor alpha
Phosphorylation drug effects
Phosphorylation physiology
Poly(ADP-ribose) Polymerases metabolism
Proto-Oncogene Proteins c-bcl-2 genetics
Proto-Oncogene Proteins c-bcl-2 metabolism
RNA, Messenger metabolism
Signal Transduction drug effects
Signal Transduction physiology
Skin Neoplasms metabolism
Skin Neoplasms pathology
Survivin
Antineoplastic Agents pharmacology
Curcumin pharmacology
Lymphoma, T-Cell drug therapy
NF-kappa B metabolism
STAT3 Transcription Factor metabolism
Skin Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1747
- Volume :
- 130
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The Journal of investigative dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 20393484
- Full Text :
- https://doi.org/10.1038/jid.2010.86