Preclinical assessment of curcumin as a potential therapy for B‐CLL

Everett, Peter C.; Meyers, John A.; Makkinje, Anthony; Rabbi, M. Ahasanur; Lerner, Adam

doi:10.1002/ajh.20757

Cited by 60 publications

(50 citation statements)

References 24 publications

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“…In this context, it is noteworthy that several other NF-B inhibitors have also shown promise in preclinical evaluation in primary CLL cells. 23,24, [43][44][45][46] The development of drug resistance is a major clinical problem in CLL. [47][48][49][50][51] Therefore, it is important to note that sensitivity to LC-1 was For personal use only.…”

Section: Discussionmentioning

confidence: 99%

The NF-κB subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target

Hewamana

Alghazal²,

Lin³

et al. 2008

Blood

143

132

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In this study, we characterized nuclear factor B (NF- B IntroductionB-cell chronic lymphocytic leukemia (CLL) is a malignancy characterized by the accumulation of CD5, CD19, and CD23 positive lymphocytes. Diagnosis is aided by the CLL immunophenotyping score which includes assessment of CD5 and CD23, FMC7, CD79b, and surface IgM. 1 Although CLL is the commonest leukemia in the Western world, it manifests a very heterogeneous clinical course, with some patients having normal age-adjusted survival, whereas the median survival for those patients with advanced stage disease is only 3 years. 2 The factors that contribute to the pathogenesis and progression of this disease are poorly understood, but decreased susceptibility to apoptosis 3 and dysregulated proliferation have been implicated. 4 Clinical studies have shown that high ZAP-70 expression, high CD38 expression, unmutated V H genes, and cytogenetic abnormalities (especially deletions of 11q and 17p) are all associated with a poor prognosis. [5][6][7][8][9] Nuclear factor B (NF-B) is a collective name for a group of inducible homodimeric and heterodimeric transcription factors made up of members of the Rel family of DNA-binding proteins. In humans, this family is composed of c-Rel, Rel B, p50, p52, and Rel A (p65) which, when bound in the cytoplasm to inhibitor of NF-B (IB) proteins, are inactive. 10,11 Various factors, including ligation of CD40 or the B-cell receptor (BCR), result in proteosomal degradation of IB releasing NF-B, which then translocates to the nucleus. 10,11 Once in the nucleus, NF-B can enhance survival by inducing apoptosis inhibitory proteins, including inhibitor of apoptosis proteins (IAPs), Fas-associated death domain (FADD)-like interleukin (IL)-1␤-converting enzyme (FLICE), and FADD-like IL-1␤-converting enzyme-inhibitory protein (FLIP). 12-14 CLL cells have been reported to exhibit high constitutive NF-B activation compared with normal B lymphocytes. [15][16][17] Although the exact factors responsible for the constitutive expression of NF-B are not fully resolved, many factors, including Akt activation, BCR signaling, CD40 ligation, IL-4, and B-cell activating factor (BAFF), have been shown to increase NF-B activity and enhance CLL cell survival, with members of the Bcl-2 family being principal transcriptional targets. [18][19][20][21][22] Several recent studies have demonstrated the proof of concept of the effectiveness of targeting NF-B in hematologic malignancies, including CLL 23,24 and acute myeloid leukemia. 25,26 In this study, we first set out to determine the range of constitutive DNA binding of NF-B within our patient cohort and to characterize the specific subunits of NF-B in these primary CLL cells. We then went on to investigate the ability of freshly isolated CLL cells to induce NF-B expression in response to BCR Submitted November 20, 2007; accepted January 25, 2008. Prepublished online as Blood First Edition paper, January 28, 2008; DOI 10.1182 DOI 10. /blood-2007 An Inside Blood analysis of this article appears at ...

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Section: Discussionmentioning

confidence: 99%

The NF-κB subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target

Hewamana

Alghazal²,

Lin³

et al. 2008

Blood

143

132

View full text Add to dashboard Cite

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“…To identify the targets of human miRNAs, we used PicTar 7 and TargetScan 8 software by following the manufacturer's instructions.…”

Section: Rna Isolationmentioning

confidence: 99%

Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells

Sun

Estrov

et al. 2008

Molecular Cancer Therapeutics

372

249

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Background: A major challenge in cancer chemotherapy has been developing safe and clinically efficacious chemotherapeutic agents. With its low toxicity profile, curcumin (diferuloylmethane), a naturally occurring flavinoid derived from the rhizome of Curcuma longa, has great promise. In vitro and in vivo preclinical studies have shown its inhibitory anticancer, antioxidant, antiinflammatory, antiproliferative, and proapoptotic activities. The multiple mechanisms of the antitumor effect of curcumin putatively include down-regulating the expression of gene products such as nuclear factor-KB, growth suppression, inducing apoptosis, and modulating various signal transduction pathways and the expression of many oncogenes. The mechanisms underlying the antitumor activity of curcumin have not, however, been completely delineated. Methods: An oligonucleotide microarray chip was developed and used to profile microRNA (miRNA) expressions in pancreatic cells treated with curcumin. Transcripts with regulated expression patterns on the arrays were validated by real-time PCRs. Additionally, potential mRNA targets were analyzed bioinformatically and confirmed with flow cytometry experiments. Results: Curcumin alters miRNA expression in human pancreatic cells, up-regulating miRNA-22 and down-regulating

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“…An online search of miR-125b targets by miRanda (http:// cbio.mskcc.org/cgi-bin/mirnaviewer/mirnaviewer.pl, [23]) and TargetScan databases (http://genes.mit. edu/ targetscan.test/ucsc.html, [24]) provided a large number of putative mRNA targets.…”

Section: Prediction and Confirmation Of Target Genes Of Mir-125bmentioning

confidence: 99%

<i>MiR-125b</i> Expression Affects the Proliferation and Apoptosis of Human Glioma Cells by Targeting <i>Bmf</i>

Xia¹,

He²,

Liu³

et al. 2009

Cell Physiol Biochem

147

110

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Background: MicroRNAs (miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell growth. Although many microRNAs were found to express in central nervous system (CNS), the role of the regulatory networks in which they are involved and their function in the pathological process of nerve cells are only just emerging. In the present study, the possible mechanisms by which one neuronal miRNAs, miR-125b, affected the growth of nervous cells were investigated using in vitro cell line model. Methods: The expression pattern of miR-125b in ATRA-treated human glioma cell lines was detected by Northern blotting and in situ localization. The effect of miR-125b on the proliferation and apoptosis of human glioma cells was analyzed by MTS assay, TUNEL and Flow cytometry analysis. In addition, the identification of target gene of miR-125b was studied by dual-luciferase activity assay and Immunoblot Analysis. Results: We found differential expression of miR-125b in 1.0 μM all-trans-retinoic acid (ATRA)-treated human glioma cell lines. Up-regulation of miR-125b partially restored cell viability and inhibited cell apoptosis in U343 cells treated by ATRA. Down-regulation of miR-125b decreased human glioma cells proliferation and enhanced the sensitivity of human glioma cells to ATRA-induced apoptosis. In addition, we found an inverse relationship between the expression of miR-125b and the cell apoptosis-related protein Bcl-2 modifying factor (Bmf), and miR-125b can interact with 3′-untranslated region (UTR) of Bmf. Conclusion: These findings indicate that overexpression of miR-125b promotes human glioma cell proliferation and inhibits ATRA-induced cell apoptosis and low expression of miR-125b sensitizes cells to ATRA-induced apoptosis. BMF may play an important role in the process of miR-125b influencing cell apoptosis.

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Preclinical assessment of curcumin as a potential therapy for B‐CLL

Cited by 60 publications

References 24 publications

The NF-κB subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target

The NF-κB subunit Rel A is associated with in vitro survival and clinical disease progression in chronic lymphocytic leukemia and represents a promising therapeutic target

Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human pancreatic cancer cells

<i>MiR-125b</i> Expression Affects the Proliferation and Apoptosis of Human Glioma Cells by Targeting <i>Bmf</i>

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