Apoptosis and Cutaneous T Cell Lymphoma

Kacinski, Barry M.; Flick, Maryann B.

doi:10.1111/j.1749-6632.2001.tb03723.x

Cited by 30 publications

(19 citation statements)

References 30 publications

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“…66 We have therefore investigated whether SDF-1 could be involved in the regulation of apoptosis of SS cells and found no significant differences between SS and healthy CD4 ϩ cells following in vitro SDF-1 stimulation.…”

Section: Discussionmentioning

confidence: 99%

Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV

Narducci

Scala

Bresin

et al. 2006

Blood

153

137

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Sé zary syndrome (SS) is a rare form of cutaneous T-cell lymphoma (CTCL) characterized by a distinct metastatic pattern mainly involving blood and skin. Chemokines and their receptors play a critical role in cellular recruitment and homing to tissues and in the metastatic process of several tumors including non-Hodgkin Tcell lymphomas (NHLs). Here we report that SS cells express a functionally active CXCR4 and that its ligand SDF-1 is abundantly produced in the skin, which represents the main destination of SS cell spreading. SDF-1 is normally inactivated by proteolytic cleavage by the CD26/ dipeptidylpeptidase IV (DPPIV). The lack of CD26 from the cell surface is a hallmark of circulating SS cells. We also show that the CD26 ؊ phenotype is maintained also in skin-infiltrating neoplastic T lymphocytes and that SS-affected individuals exhibit a reduced activity of plasma soluble CD26. Finally, we observe that the addition of soluble CD26 reduces the migratory response of SS cells to SDF-1 whereas the inhibition of the CD26 peptidase activity in Hut78, a CD26 ؉ CTCL cell line, enhances the SDF-1-induced migration of these cells. Our findings suggest that the SDF-1-CXCR4 axis could play an important role in skin homing of SS through the regulatory activity of CD26. IntroductionCutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas (NHLs) that show a considerable variability in clinical presentation, histology, immunophenotype, and prognosis. They represent a clonal malignancy 1 of CD4 ϩ helper T cells 2,3 with a memory phenotype 4 and tendency to accumulate in the skin. 5 Mycosis fungoides (MF) and Sézary syndrome (SS) are the 2 major clinical variants of CTCLs. While MF shows a skinrestricted infiltration of the clonal T-cell population and an indolent course, SS is a leukemic and erythrodermic variant of CTCL characterized by the presence of tumor lymphocytes in the skin, lymph nodes, and peripheral blood. These tumor cells, named SS cells, have major abnormalities like a low mitotic index, aberrant but nonuniform chromosomal alterations, 6 monoclonal rearrangement 7 with a loss of T-cell receptor repertoire complexity 8 and loss of surface molecules such as CD7, CD26, and CD49d. 9-11 SS cells mainly localize to the skin and express cutaneous lymphocyteassociated antigen (CLA) that has been implicated in skin-specific homing patterns. 4,9 However, the mechanisms underlying the accumulation of these atypical lymphocytes to the skin are poorly defined. Extravasation and active locomotion of malignant lymphocytes could suggest the involvement of secreted factors such as chemokines. Chemokines regulate multiple cell functions, including cell chemotaxis, proliferation, and apoptosis, and are involved in leukocyte transendothelial migration and homing to tissues.These biologic activities are mediated through their interaction with G protein-coupled chemokine receptors expressed by target cells such as leukocytes, hematopoietic cells, neuronal cells, glial cells, and cells of the vasculat...

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Section: Discussionmentioning

confidence: 99%

Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV

Narducci

Scala

Bresin

et al. 2006

Blood

153

137

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“…Sézary syndrome (SS), a leukemic variant, is characterized with erythroderma and atypical cells in the peripheral blood and by a peripheral blood T-cell clone (Duvic and Foss, 2007). These malignant T cells exhibit abnormal apoptotic mechanisms, such as loss of Fas or expression of bcl-2, which result in the loss of activationinduced cell death, prolonged life span, and accumulation (Kacinski and Flick, 2001). There are a limited number of Food and Drug Administration-approved therapeutic modalities available to treat patients with MF/SS, including bexarotene, intravenous denileukin diftitox, photopheresis, and vorinostat (Duvic et al, 2001Duvic and Foss, 2007).…”

Section: Introductionmentioning

confidence: 99%

Curcumin Selectively Induces Apoptosis in Cutaneous T-Cell Lymphoma Cell Lines and Patients’ PBMCs: Potential Role for STAT-3 and NF-κB Signaling

Zhang

et al. 2010

Journal of Investigative Dermatology

105

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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.

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“…These cell lines were cultured in RPMI-1640 medium supplemented with 10% heat-inactivated FBS, GIBCO (16). Curcumin, N-acetyl-Lcysteine (NAC), rapamycin, 3-methyladenine (3-MA), wortmannin, propidium iodide (PI), 3,3 0 -dihexyloxacarbocyanine iodide (DiOC 6 ), anti-actin antibody, antimouse horseradish peroxidase antibody, and anti-rabbit horseradish peroxidase antibody were purchased from Sigma. Dihydroethidium and Amplex Red Hydrogen Peroxide/Peroxidase Assay Kit were purchased from Molecular Probes (Invitrogen).…”

Section: Cell Culture and Reagentsmentioning

confidence: 99%

“…The 2 main forms are mycosis fungoides and its leukemic counterpart S ezary syndrome (1,2). Defective T-cell apoptosis and constitutive activation of NF-kB contribute to the pathogenesis of CTCLs (2,3). NF-kB is a regulator of many genes involved in inflammation, cell proliferation, and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

Khan

Gahlot

Majumdar

2012

Molecular Cancer Therapeutics

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Curcumin is known to exert its anticancer effect either by scavenging or by generating reactive oxygen species (ROS). In this study, we report that curcumin-mediated rapid generation of ROS induces apoptosis by modulating different cell survival and cell death pathways in HuT-78 cells. Curcumin induces the activation of caspase-8, -2, and -9, alteration of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3 and concomitant PARP cleavage, but the addition of caspase inhibitors only partially blocked the curcumin-mediated apoptosis. Curcumin also downregulates the expression of antiapoptotic proteins c-FLIP, Bcl-xL, cellular inhibitor of apoptosis protein, and X-linked IAP in a ROS-dependent manner. Curcumin disrupts the integrity of IKK and beclin-1 by degrading Hsp90. Degradation of IKK leads to the inhibition of constitutive NF-kB. Degradation of beclin-1 by curcumin leads to the accumulation of autophagy-specific marker, microtubule-associated protein-I light chain 3 (LC3), LC3-I. Our findings indicate that HuT-78 cells are vulnerable to oxidative stress induced by curcumin and as a result eventually undergo cell death. Mol Cancer Ther; 11(9); 1873-83. Ó2012 AACR.

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Apoptosis and Cutaneous T Cell Lymphoma

Cited by 30 publications

References 30 publications

Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV

Skin homing of Sézary cells involves SDF-1-CXCR4 signaling and down-regulation of CD26/dipeptidylpeptidase IV

Curcumin Selectively Induces Apoptosis in Cutaneous T-Cell Lymphoma Cell Lines and Patients’ PBMCs: Potential Role for STAT-3 and NF-κB Signaling

Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets

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