Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation

Mukhopadhyay, Asok; Banerjee, Sanjeev; Stafford, Lewis J.; Xia, Chunzhi; Liu, Mingyao; Aggarwal, Bharat B.

doi:10.1038/sj.onc.1206048

Cited by 303 publications

(197 citation statements)

References 45 publications

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“…A recent report showed that curcumin induces proteasomal malfunction and accumulation of ubiquitinated protein such as p53 (33). However, contrasting results were reported by others (34), which have shown the down-regulation of cyclin D1 protein by curcumin through promoting proteolysis. From these reports, we speculated possible explanations for HIF-1· destabilization by curcumin.…”

Section: Discussionmentioning

confidence: 51%

Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1

Bae

Kim²,

Jeong³

et al. 2006

Oncol Rep

106

103

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Abstract. Hypoxia-inducible factor-1 (HIF-1) has a central role in cellular responses to hypoxia, including the transcriptional activation of a number of genes involved in angiogenesis in tumors. We found that curcumin, a natural, biologically active compound isolated from the commonly used spice turmeric, significantly decreases hypoxia-induced HIF-1· protein levels in HepG2 hepatocellular carcinoma cells. Moreover, curcumin suppressed the transcriptional activity of HIF-1 under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major HIF-1 target angiogenic factor. Curcumin also blocked hypoxia-stimulated angiogenesis in vitro and down-regulated HIF-1· and VEGF expression in vascular endothelial cells. These findings suggest that curcumin may play pivotal roles in tumor suppression via the inhibition of HIF-1·-mediated angiogenesis.

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Section: Discussionmentioning

confidence: 51%

Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1

Bae

Kim²,

Jeong³

et al. 2006

Oncol Rep

106

103

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“…Consistent with the present results, earlier studies show that various anti-angiogenic molecules, such as endostatin, capsaicin and curcumin, inhibit Rb phosphorylation and DNA synthesis of endothelial cells through downregulation of cyclin D1. 40,41 On the contrary, treatment of emodin in bovine aortic endothelial cells induced G2/M phase arrest of cell cycle. 38 Our experiment also showed G2/M phase arrest by emodin in HUVECs; however, its concentration was higher enough for inducing cell death.…”

Section: Discussionmentioning

confidence: 99%

Emodin inhibits vascular endothelial growth factor‐A‐induced angiogenesis by blocking receptor‐2 (KDR/Flk‐1) phosphorylation

Kwak

Park

et al. 2006

Intl Journal of Cancer

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Emodin (1,3,8‐trihydroxy‐6‐methylanthraquinone), an active component in the root and rhizome of Rheum palmatum, is a tyrosine kinase inhibitor with a number of biological activities, including antitumor effects. Here, we examine the effects of emodin on vascular endothelial growth factor (VEGF)‐A‐induced angiogenesis, both in vitro and in vivo. In vitro, emodin dose‐dependently inhibits proliferation, migration into the denuded area, invasion through a layer of Matrigel and tube formation of human umbilical vein endothelial cells (HUVECs) stimulated with VEGF‐A. Emodin also inhibits basic fibroblast growth factor‐induced proliferation and migration of HUVECs and VEGF‐A‐induced tube formation of human dermal microvascular endothelial cells. Specifically, emodin induces the cell cycle arrest of HUVECs in the G0/G1 phase by suppressing cyclin D1 and E expression and retinoblastoma protein phosphorylation, and suppresses Matrigel invasion by inhibiting the basal secretion of matrix metalloproteinase‐2 and VEGF‐A‐stimulated urokinase plasminogen activator receptor expression. Additionally, emodin effectively inhibits phosphorylation of VEGF‐A receptor‐2 (KDR/Flk‐1) and downstream effector molecules, including focal adhesion kinase, extracellular signal‐regulated kinase 1/2, p38 mitogen‐activated protein kinase, Akt and endothelial nitric oxide synthase. In vivo, emodin strongly suppresses neovessel formation in the chorioallantoic membrane of chick and VEGF‐A‐induced angiogenesis of the Matrigel plug in mice. Our data collectively demonstrate that emodin effectively inhibits VEGF‐A‐induced angiogenesis in vitro and in vivo. Moreover, inhibition of phosphorylation of KDR/Flk‐1 and downstream effector molecules is a possible underlying mechanism of the anti‐angiogenic activity of emodin. Based on these data, we propose that an interaction of emodin with KDR/Flk‐1 may be involved in the inhibitory function of emodin toward VEGF‐A‐induced angiogenesis in vitro and responsible for its potent anti‐angiogenic in vivo. © 2006 Wiley‐Liss, Inc.

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“…In the current study, BA decreased the expression of five major cyclin proteins, all presumably playing significant roles in cell cycle progression (Figure 2A). Furthermore, the ability of antiproliferative agents to inhibit the expression of these proteins is important, since cyclins A, B1, E, and D1 have been correlated with prostate cancer aggressiveness (Mukhopadhyay et al, 2002;Maddison et al, 2004;Tsao et al, 2004).…”

Section: Proliferationmentioning

confidence: 99%

Cellular changes in boric acid-treated DU-145 prostate cancer cells

Barranco

Eckhert

2006

Br J Cancer

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Epidemiological, animal, and cell culture studies have identified boron as a chemopreventative agent in prostate cancer. The present objective was to identify boron-induced changes in the DU-145 human prostate cancer cell line. We show that prolonged exposure to pharmacologically-relevant levels of boric acid, the naturally occurring form of boron circulating in human plasma, induces the following morphological changes in cells: increases in granularity and intracellular vesicle content, enhanced cell spreading and decreased cell volume. Documented increases in b-galactosidase activity suggest that boric acid induces conversion to a senescentlike cellular phenotype. Boric acid also causes a dose-dependent reduction in cyclins A -E, as well as MAPK proteins, suggesting their contribution to proliferative inhibition. Furthermore, treated cells display reduced adhesion, migration and invasion potential, along with F-actin changes indicative of reduced metastatic potential. Finally, the observation of media acidosis in treated cells correlated with an accumulation of lysosome-associated membrane protein type 2 (LAMP-2)-negative acidic compartments. The challenge of future studies will be to identify the underlying mechanism responsible for the observed cellular responses to this natural blood constituent.

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Curcumin-induced suppression of cell proliferation correlates with down-regulation of cyclin D1 expression and CDK4-mediated retinoblastoma protein phosphorylation

Cited by 303 publications

References 45 publications

Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1

Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1

Emodin inhibits vascular endothelial growth factor‐A‐induced angiogenesis by blocking receptor‐2 (KDR/Flk‐1) phosphorylation

Cellular changes in boric acid-treated DU-145 prostate cancer cells

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