Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53

Park, Jong Bae; Kim, Eun‐Hee; Park, In-Chul; Lee, Hyung-Chan; Woo, Sang-Hyeok; Lee, Jae-Young; Hong, Yoo Jin; Rhee, Chang Hun; Choi, Su-Mi; Shim, Bum-Sang; Lee, Seung‐Hoon; Hong, Seok‐Il

doi:10.3892/ijo.21.2.379

Cited by 63 publications

(56 citation statements)

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“…It was shown by others that p27 expression was suppressed in Bcr-Ablexpressing cells via the phosphoinositol-3-kinase/Akt pathway (20), and inhibition of Bcr-Abl tyrosine kinase activity with STI-571 rapidly increased p27 protein level (42). There are only a few articles showing p27 up-regulation after curcumin treatment (39,43), and our data are in line with those.…”

Section: Discussionsupporting

confidence: 91%

Curcumin Affects Components of the Chromosomal Passenger Complex and Induces Mitotic Catastrophe in Apoptosis-Resistant Bcr-Abl-Expressing Cells

Wolanin

Magalska

Mosieniak

et al. 2006

Molecular Cancer Research

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The Bcr-Abl oncoprotein plays a major role in the development and progression of chronic myeloid leukemia and is a determinant of chemotherapy resistance occurring during the blast crisis phase of the disease. The aim of this article was to investigate the possibility of combating the resistance to apoptosis caused by Bcr-Abl by inducing an alternative cell death process. As a model of chronic myeloid leukemia, we employed Bcr-Abl-transfected mouse progenitor 32D cells with low and high Bcr-Abl expression levels corresponding to drug-sensitive and drug-resistant cells, respectively. The drug curcumin (diferuloylmethane), a known potent inducer of cell death in many cancer cells, was investigated for efficacy with Bcr-Abl-expressing cells. Curcumin strongly inhibited cell proliferation and affected cell viability by inducing apoptotic symptoms in all tested cells; however, apoptosis was a relatively late event. G 2 -M cell cycle arrest, together with increased mitotic index and cellular and nuclear morphology resembling those described for mitotic catastrophe, was observed and preceded caspase-3 activation and DNA fragmentation. Mitosis-arrested cells displayed abnormal chromatin organization, multipolar chromosome segregation, aberrant cytokinesis, and multinucleated cellsmorphologic changes typical of mitotic catastrophe. We found that the mitotic cell death symptoms correlated with attenuated expression of survivin, a member of the chromosomal passenger complex, and mislocalization of Aurora B, the partner of survivin in the chromosomal passenger complex. Inhibition of survivin expression with small interfering RNA exhibited similar mitotic disturbances, thus implicating survivin as a major, albeit not the only, target for curcumin action.This study shows that curcumin can overcome the broad resistance to cell death caused by expression of Bcr-Abl and suggests that curcumin may be a promising agent for new combination regimens for drug-resistant chronic myeloid leukemia.

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Section: Discussionsupporting

confidence: 91%

Curcumin Affects Components of the Chromosomal Passenger Complex and Induces Mitotic Catastrophe in Apoptosis-Resistant Bcr-Abl-Expressing Cells

Wolanin

Magalska

Mosieniak

et al. 2006

Molecular Cancer Research

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“…Exposure of certain human cancer cells to curcumin results in a G 1 cell cycle arrest (30), and treatment of human cells with other iron chelators also induces a reversible G 1 cell cycle arrest (3,29). To extend the observations made in yeast, we further explored the effects of curcumin on cell growth by treating human osteosarcoma U2OS cells with curcumin and monitoring cell density relative to that of a DMSO drug vector control.…”

Section: Downloaded Frommentioning

confidence: 99%

Curcumin Inhibits Growth of Saccharomyces cerevisiae through Iron Chelation

et al. 2011

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Curcumin, a polyphenol derived from turmeric, is an ancient therapeutic used in India for centuries to treat a wide array of ailments. Interest in curcumin has increased recently, with ongoing clinical trials exploring curcumin as an anticancer therapy and as a protectant against neurodegenerative diseases. In vitro, curcumin chelates metal ions. However, although diverse physiological effects have been documented for this compound, curcumin's mechanism of action on mammalian cells remains unclear. This study uses yeast as a model eukaryotic system to dissect the biological activity of curcumin. We found that yeast mutants lacking genes required for iron and copper homeostasis are hypersensitive to curcumin and that iron supplementation rescues this sensitivity. Curcumin penetrates yeast cells, concentrates in the endoplasmic reticulum (ER) membranes, and reduces the intracellular iron pool. Curcumin-treated, iron-starved cultures are enriched in unbudded cells, suggesting that the G 1 phase of the cell cycle is lengthened. A delay in cell cycle progression could, in part, explain the antitumorigenic properties associated with curcumin. We also demonstrate that curcumin causes a growth lag in cultured human cells that is remediated by the addition of exogenous iron. These findings suggest that curcumin-induced iron starvation is conserved from yeast to humans and underlies curcumin's medicinal properties.Curcumin is the major chemical component of turmeric, a dietary spice made from the root of the Curcuma longa Linn plant and used extensively in traditional Indian medicine (38). Curcumin is a potent bioactive compound that is used to treat cancer (5, 35), atherosclerosis (33), and neurodegenerative diseases, such as Alzheimer's (26, 45) and Parkinson's (44) disease, as well as to promote wound healing (15,36). Curcumin is particularly appealing as a therapeutic agent because of its extremely low toxicity. Many biological activities have been ascribed to curcumin. For example, curcumin suppresses inflammatory responses in cultured cells and in animals and also exhibits antioxidant properties. Furthermore, curcumin's ability to inhibit tumorigenesis and proliferation of a wide variety of cancerous cells has been well documented. Curcumin is a polyphenol and complexes readily with a number of different metal ions. In aqueous solutions of neutral pH, curcumin is an effective chelator of Fe(III) (2). Curcumin is also lipophilic and readily crosses membranes (19), so therefore it may also chelate metal ions intracellularly. How these chemical properties contribute to curcumin's biological activities, however, is not understood.Identifying relevant in vivo targets of small molecules is technically challenging. Recently, several genetic and genomic approaches have been developed that use the simple eukaryote Saccharomyces cerevisiae, or budding yeast, to study the mechanism of drug action (17,27,31). One such method, termed homozygous profiling, uses a comprehensive collection of 4,700 homozygous diploid deletion yeast...

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“…Cyclooxygenase-2, which is overexpressed in colorectal cancers through NF-nB or activator protein-1 transactivation, is also suppressed by curcumin (7), and other cyclooxygenase-2 inhibitors are known to have chemopreventive and antiangiogenic properties (4). Curcumin has been shown to arrest the cell cycle at G 0 -G 1 or G 2 -M through up-regulation of the cyclin-dependent kinase inhibitors p21 and p27 and down-regulation of Cdc2 and cyclin B1 (8). Curcumin blocks growth factor signaling via inhibition of tyrosine kinase activity or depletion of ErbB-2 (9).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer

Ohori

Yamakoshi

Tomizawa

et al. 2006

Molecular Cancer Therapeutics

224

167

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Curcumin (diferuloylmethane) is a dietary phytochemical with low toxicity that exhibits growth-suppressive activity against a variety of cancer cells and possesses certain chemopreventive properties. Curcumin has already been the subject of several clinical trials for use as a treatment in human cancers. Synthetic chemical modifications of curcumin have been studied intensively in an attempt to find a molecule with similar but enhanced properties of curcumin. In this study, a series of novel curcumin analogues were synthesized and screened for anticancer activity. New analogues that exhibit growth-suppressive activity 30 times that of curcumin and other commonly used anticancer drugs were identified. Structurally, the new analogues are symmetrical 1,5-diarylpentadienone whose aromatic rings possess an alkoxy substitution at each of the positions 3 and 5. Analysis of the effects of the analogues on the expression of cancer-related genes usually affected by curcumin indicated that some induced the down-regulation of B-catenin, Ki-ras, cyclin D1, c-Myc, and ErbB-2 at as low as one eighth the concentration at which curcumin normally has an effect. The analogues,

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Curcumin inhibits cell cycle progression of immortalized human umbilical vein endothelial (ECV304) cells by up-regulating cyclin-dependent kinase inhibitor, p21WAF1/CIP1, p27KIP1 and p53

Cited by 63 publications

References 0 publications

Curcumin Affects Components of the Chromosomal Passenger Complex and Induces Mitotic Catastrophe in Apoptosis-Resistant Bcr-Abl-Expressing Cells

Curcumin Affects Components of the Chromosomal Passenger Complex and Induces Mitotic Catastrophe in Apoptosis-Resistant Bcr-Abl-Expressing Cells

Curcumin Inhibits Growth of Saccharomyces cerevisiae through Iron Chelation

Synthesis and biological analysis of new curcumin analogues bearing an enhanced potential for the medicinal treatment of cancer

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