Curcumin Causes the Growth Arrest and Apoptosis of B Cell Lymphoma by Downregulation of egr-1, C-myc, Bcl-XL, NF-κB, and p53

Han, Seong‐Su; Chung, Seung-Tae; Robertson, Darrell A.; Ranjan, Dinesh; Bondada, Subbarao

doi:10.1006/clim.1999.4769

Cited by 196 publications

(123 citation statements)

References 45 publications

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“…Curcumin has been shown to inhibit the NF-B pathway in many cancer cells including multiple myeloma (11,12). Accordingly, we found that Bcl-x L is down-regulated in OCI-Ly10 and WEHI-231 cell lines upon treatment with curcumin suggesting that curcumin targets the NF-B pathway in B lymphoma cells (Fig.…”

Section: Overexpression Of Bcl-x L Overcomes Curcumin-induced Apoptosismentioning

confidence: 59%

“…Previous studies from our laboratory demonstrated that curcumin induced both apoptosis and growth arrest (12). Current studies using caspase inhibitor and the Bcl-x L overexpressing cell line suggests that apoptosis is the primary mechanism of curcumininduced growth inhibition.…”

Section: Discussionmentioning

confidence: 92%

“…Previously, we have shown that low doses of curcumin inhibit the proliferation of murine B lymphoma, BKS-2, but not that of normal B cells (12). The effect of curcumin was partially reversed by stimulation with CpG oligonucleotides or by ligation of CD40.…”

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confidence: 89%

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Spleen Tyrosine Kinase (Syk), a Novel Target of Curcumin, Is Required for B Lymphoma Growth

Gururajan

Dasu

Shahidain

et al. 2007

The Journal of Immunology

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Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-xL, a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

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Section: Overexpression Of Bcl-x L Overcomes Curcumin-induced Apoptosismentioning

confidence: 59%

Section: Discussionmentioning

confidence: 92%

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Spleen Tyrosine Kinase (Syk), a Novel Target of Curcumin, Is Required for B Lymphoma Growth

Gururajan

Dasu

Shahidain

et al. 2007

The Journal of Immunology

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“…In studies of the myeloid cell line ML-1a, Singh and Aggarwal reported that curcumin inhibited IkBa phosphorylation, degradation, and NF-kB translocation induced by a diverse range of stimuli including TNF, hydrogen peroxide, and phorbol esters [2]. Subsequent studies confirmed curcumininduced inhibition of NF-kB translocation in multiple cell types, including colon [3], gastric [4], pancreatic [5], and squamous epithelial tumor cell lines [6] as well as B-cell lymphoma and multiple myeloma cell lines [7,8]. Although the precise mechanism by which NF-kB translocation is inhibited remains unclear, Plummer et al demonstrated that curcumin reduced NF-kB translocation in HEK293 cells transfected with NIK, IKKa, or IKKb kinases [3].…”

Section: Introductionmentioning

confidence: 92%

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

et al. 2006

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Curcumin, the principle component of the spice turmeric, has been used as an anti-inflammatory medication in India and China for centuries. Recent studies, predominantly using actively dividing cell lines, have suggested that this compound could be used as a chemopreventative or therapeutic agent for epithelial tumors. As curcumin has been reported to inhibit the NIK/IKK complex, an activity that would be expected to induce apoptosis in B cell malignancies, we sought to determine whether curcumin induces apoptosis in vitro in primary chronic lymphocytic leukemia (B-CLL) cells. Primary leukemic cells were incubated with varying dosages of curcumin, followed by assessment for apoptosis. The role of PPARg or NF-kB signaling in curcumin-induced apoptosis was examined by cotreatment with a PPARg antagonist or EMSA of nuclear NFkB complexes. We also examined whether a clinically achievable concentration of curcumin (1 mM) would augment the apoptotic effects of fludarabine, dexamethasone, vincristine or the PDE4 inhibitor rolipram. In B-CLL cells from 14 patients, curcumin-induced apoptosis with a mean EC 50 of 5.5 mM. In contrast, the EC 50 for whole mononuclear cells from a healthy donor was 21.8 mM. In a 48 hr wash-out time course, curcumin-induced apoptosis was time-dependent, with a substantial reduction in apoptosis observed when curcumin was removed after 5 hr. Curcumin treatment reduced basal nuclear NF-kB levels and 1 mM curcumin augmented both vinca alkaloid and PDE4 inhibitor-induced apoptosis in B-CLL cells. Our studies suggest that curcumin may augment the efficacy of established or experimental therapies for B-CLL. Am. J. Hematol. 82:23-30, 2007. V V C 2006 Wiley-Liss, Inc.

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“…In addition to its role as a spice, curcumin has also been used for centuries to treat inflammatory disorders (16). Although the exact mechanism of action for curcumin is not well understood, it has been shown to prevent inhibitory factor I B degradation, retaining NF-B in the cytoplasm in its inactive form and to inhibit activation of c-Jun N-terminal kinase (17)(18)(19). In addition to its anti-inflammatory properties, curcumin induces the growth arrest and apoptosis of a number of different tumor cell lines, also possibly through an interaction with the NF-B signaling pathway (18 -20).…”

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confidence: 99%

Curcumin Inhibits Activation of Vγ9Vδ2 T Cells by Phosphoantigens and Induces Apoptosis Involving Apoptosis-Inducing Factor and Large Scale DNA Fragmentation

Cipriani

Borsellino

Knowles

et al. 2001

The Journal of Immunology

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Curcumin, in addition to its role as a spice, has been used for centuries to treat inflammatory disorders. Although the mechanism of action remains unclear, it has been shown to inhibit the activation of NF-κB and AP-1, transcription factors required for induction of many proinflammatory mediators. Due to its low toxicity it is currently under consideration as a broad anti-inflammatory, anti-tumor cell agent. In this study we investigated whether curcumin inhibited the response of γδ T cells to protease-resistant phosphorylated derivatives found in the cell wall of many pathogens. The results showed that curcumin levels ≥30 μM profoundly inhibited isopentenyl pyrophosphate-induced release of the chemokines macrophage inflammatory protein-1α and -1β and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-κB and AP-1. Commencing around 16 h, treatment with curcumin lead to the induction of cell death that could not be reversed by APC, IL-15, or IL-2. This cytotoxicity was associated with increased annexin V reactivity, nuclear expression of active caspase-3, cleavage of poly(ADP-ribose) polymerase, translocation of apoptosis-inducing factor to the nucleus, and morphological evidence of nuclear disintegration. However, curcumin led to only large scale DNA chromatolysis, as determined by a combination of TUNEL staining and pulse-field and agarose gel electrophoresis, suggesting a predominantly apoptosis-inducing factor-mediated cell death process. We conclude that γδ T cells activated by these ubiquitous Ags are highly sensitive to curcumin, and that this effect may contribute to the anti-inflammatory properties of this compound.

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Curcumin Causes the Growth Arrest and Apoptosis of B Cell Lymphoma by Downregulation of egr-1, C-myc, Bcl-XL, NF-κB, and p53

Cited by 196 publications

References 45 publications

Spleen Tyrosine Kinase (Syk), a Novel Target of Curcumin, Is Required for B Lymphoma Growth

Spleen Tyrosine Kinase (Syk), a Novel Target of Curcumin, Is Required for B Lymphoma Growth

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

Curcumin Inhibits Activation of Vγ9Vδ2 T Cells by Phosphoantigens and Induces Apoptosis Involving Apoptosis-Inducing Factor and Large Scale DNA Fragmentation

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