Deguelin inhibits expression of IκBα protein and induces apoptosis of B-CLL cells in vitro

Geeraerts, Ben; Vanhoecke, Barbara; Berghe, Wim Vanden; Philippé, Jan; Offner, Fritz; Deforce, Dieter

doi:10.1038/sj.leu.2404788

Cited by 25 publications

(19 citation statements)

References 52 publications

(60 reference statements)

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“…The results of fluorescence microscopic examination also revealed features characteristic of apoptosis, confirming the ability of deguelin to induce apoptosis in MPC-11 cells. Consistent with our results, other groups reported that deguelin induced apoptosis in various types of cells, including colon cancer, gastric cancer, leukemia, breast cancer and hepatic cancer cells (7,8,(17)(18)(19).…”

Section: Discussionsupporting

confidence: 92%

Deguelin, a natural rotenoid, inhibits mouse myeloma cell growth in vitro via induction of apoptosis

et al. 2012

Oncology Letters

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Abstract. Deguelin is a naturally occurring rotenoid with strong cancer chemopreventive and antitumor activities. In the present study, we investigated the antitumor activity of deguelin against MPC-11 murine myeloma cells and the possible mechanism of action in vitro. Our results revealed that deguelin inhibited the proliferation of MPC-11 cells in a concentration-and time-dependent manner and caused the apoptotic death of MPC-11 cells. Following exposure to deguelin, the phosphorylation of Akt was decreased. The inhibition of cell growth may be associated with decreased levels of phosphorylated Akt. Deguelin-induced apoptosis was characterized by the upregulation of Bax, downregulation of Bcl-2 and activation of caspase-3. In conclusion, deguelin inhibits murine myeloma cell proliferation by inducing apoptosis via regulation of the Bax/Bcl-2 ratio and by inhibition of the activation of Akt. Its potential as an anticancer agent against multiple myeloma warrants further investigation.

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Section: Discussionsupporting

confidence: 92%

Deguelin, a natural rotenoid, inhibits mouse myeloma cell growth in vitro via induction of apoptosis

et al. 2012

Oncology Letters

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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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“…It also increases the sensitivity of leukemia cells to chemotherapeutic agents (7) and suppresses the growth of human colon cancer cells (8). Deguelin blocks the proliferation of premalignant and malignant human bronchial epithelial (HBE) cells by inducing apoptosis (9).…”

Section: Introductionmentioning

confidence: 99%

Deguelin promotes apoptosis and inhibits angiogenesis of gastric cancer

Li¹

2010

Oncol Rep

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Abstract. Gastric cancer is often diagnosed in locally advanced or metastatic stages, which preludes a poor prognosis. As only 10% of patients with advanced gastric cancer treated with chemotherapy survive 2 years, new approaches for preventing and controlling the disease are required. We therefore, assessed in gastric cancer cells the chemotherapeutic potential and mechanism of deguelin, a rotenoid of the flavonoid family isolated from several plant species. The effect of deguelin on the proliferation and apoptosis in the gastric cancer cells were assessed by MTT and flow cytometry. The growth of gastric cancer cells (SNU-484, AGS and MKN-28) was inhibited by deguelin in a dose-dependent manner. G 2 /M phase arrest was induced by deguelin in gastric cancer cells. Deguelin (1 μM) induced chromatin condensation and DNA fragmentation. Also the exposure to 1 μM deguelin resulted in the increase in earlyapoptotic cells (Annexin V-positive/Propidium iodidenegative) after 24 h, compared to the cells in the control medium (31 versus 12%). Deguelin-induced apoptosis involved the caspase-9 and caspase-3 pathways in gastric cancer cells. Akt phosphorylation, hypoxia-inducible factor-1· accumulation, and vascular endothelial growth factor expression in gastric cancer cells was inhibited by deguelin. Taken together, deguelin showed anticancer activity in gastric cancer cells, which is correlated with the inhibition of angiogenesis and induction of apoptosis. Deguelin may be a potential agent in inhibiting the progression of gastric cancer by virtue of its activity on these crucial cell characteristics.

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Deguelin inhibits expression of IκBα protein and induces apoptosis of B-CLL cells in vitro

Cited by 25 publications

References 52 publications

Deguelin, a natural rotenoid, inhibits mouse myeloma cell growth in vitro via induction of apoptosis

Deguelin, a natural rotenoid, inhibits mouse myeloma cell growth in vitro via induction of apoptosis

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

Deguelin promotes apoptosis and inhibits angiogenesis of gastric cancer

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