Curcumin as a DNA Topoisomerase II Poison

Martı́n-Cordero, Carmen; López‐Lázaro, Miguel; Gálvez, Marina; Ayuso, Marı́a Jesús

doi:10.1080/14756360310001613085

Cited by 99 publications

(68 citation statements)

References 32 publications

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“…These chemical groups are known to react covalently with exposed thiol groups of cysteine residues of proteins through a reaction termed Michael addition. This reaction may explain, for instance, why curcumin generates ROS by irreversibly modifying the antioxidant enzyme thioredoxin reductase, 49 why curcumin induces topoisomerase II-mediated DNA damage, 10,54,55 and why curcumin inactivates the tumor suppressor protein p53. 56,57 Several other lines of evidence raise concern about curcumin safety.…”

Section: Dear Editormentioning

confidence: 99%

The dark side of curcumin

Burgos-Morón

Calderón-Montaño

Salvador

et al. 2010

Intl Journal of Cancer

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Dear Editor,Curcumin is a yellow-orange pigment obtained from the plant Curcuma longa. The powdered rhizome of this plant, called turmeric, is a common ingredient in curry powders and has a long history of use in traditional Asian medicine for a wide variety of disorders. In the last decade a large number of reports have been published on the beneficial effects of curcumin, and it has repeatedly been claimed that this natural product is efficient and safe for the prevention and treatment of several diseases including cancer. 1-3 It is not surprising, therefore, that curcumin is currently sold as a dietary supplement and that numerous clinical trials are ongoing or recruiting participants to evaluate curcumin activity. But there is accumulating evidence that curcumin may not be so effective and safe. Because such evidence is not generally acknowledged, the purpose of this letter is to briefly review the negative properties of curcumin so that they can be balanced against its beneficial effects.Most of the evidence that supports the therapeutic potential of curcumin is mainly based on in vitro studies in which curcumin was tested at concentrations in the micromolar range. Several reports have demonstrated, however, that the plasma concentrations of curcumin in people taking relatively high oral doses of this compound are very low, typically in the nanomolar range (reviewed in Ref. 4). For instance, a recent study examined the pharmacokinetics of a curcumin preparation in 12 healthy human volunteers 0.25-72 hr after an oral dose of 10 or 12 g. Using a high-performance liquid chromatography assay with a limit of detection of 50 ng mL À1 , only 1 subject had detectable free curcumin at any of the time points assayed. 5 The fact that curcumin also undergoes extensive metabolism in intestine and liver 6,7 means that high concentrations of curcumin cannot be achieved and maintained in plasma and tissues after oral ingestion. This is a major obstacle for the clinical development of this agent and suggests that the therapeutic potential of oral curcumin is limited. The low clinical efficiency of curcumin in the treatment of several chronic diseases such as Alzheimer's disease and cardiovascular diseases has been discussed recently. 8 As far as cancer is concerned, in vitro studies have demonstrated that cancer cells do not die unless they are exposed to curcumin concentrations of 5-50 lM for several hours. 4,9,10 Because of its poor bioavailability, these concentrations are not achieved outside the gastrointestinal tract when curcumin is taken orally. Because of its extensive metabolism in intestine and liver, these concentrations cannot be maintained for several hours in the gastrointestinal tract. This suggests that the chemotherapeutic potential of oral curcumin is limited even for the treatment of cancers of the gastrointestinal tract. Accordingly, when 15 patients with advanced colorectal cancer were treated with curcumin at daily doses of 3.6 g for up to 4 months, no partial responses to treatment or decreases in tu...

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Section: Dear Editormentioning

confidence: 99%

The dark side of curcumin

Burgos-Morón

Calderón-Montaño

Salvador

et al. 2010

Intl Journal of Cancer

Self Cite

296

210

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“…Many reports in recent years have shown that numerous naturally occurring and synthetic compounds with cytotoxic potential exert, in part, their functions through the inhibition of DNA topoisomerase enzymes [5,6,10,11]. The ability of specific agents to interfere with the catalytic cycle of topo I and stabilize the covalent complex can be biochemically addressed in sc plasmid DNA relaxation or in lineaer DNA cleavage assays [8].…”

Section: Resultsmentioning

confidence: 99%

“…Type II topoisomerases (Topo II), on the other hand, create transient breaks in both strands of a duplex, pass an intact DNA segment through the break and then reseal the cleavage site [7,8]. Over the past years, DNA topoisomerases have been recognized as an effective approach for the development of chemotherapeutics [5,6,[9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic activity of 4′-hydroxychalcone derivatives against Jurkat cells and their effects on mammalian DNA topoisomerase I

Gül

Cizmecioglu

Zencir

et al. 2009

Journal of Enzyme Inhibition and Medicinal Chemistry

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Chalcones (1,3-diaryl-2-propen-1-ones) are a, b-unsaturated ketones with cytotoxic and anticancer properties. Several reports have shown that compounds with cytotoxic properties may also interfere with DNA topoisomerase functions. Five derivatives of 4 0 -hydroxychalcones were examined for cytotoxicity against transformed human T (Jurkat) cells as well as plasmid supercoil relaxation experiments using mammalian DNA topoisomerase I. The compounds were 3-phenyl-1-(4, and 3-(2-thienyl)-1-(4 0 -hydroxyphenyl)-2-propen-1-one (V). The order of the cytotoxicity of the compounds was; IV > III > II > I > V. Compound IV, had the highest Hammett and log P values (0.23 and 4.21, respectively) and exerted both highest cytotoxicity and strongest DNA topoisomerase I inhibition. Compounds I and II gave moderate interference with the DNA topoisomerase I while III & V did not interfere with the enzyme.

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“…In this point, the apoptosis could be either mitochondria-dependent or mitochondriaindependent as shown in Figure 4. It is also reported that curcumin induces apoptotic cell death by DNAdamage in human cancer cell lines, TK-10, MCF-7 and UACC-62 by acting as topoisomerase II poison (28).…”

Section: Anticarcinogenic Effects Of Curcuminmentioning

confidence: 99%

Turmeric Curcuminoid Polyphenolics as Antioxidant and Anticarcinogenic Agents

Tokuşoğlu

Simsek²,

Parvizi³

et al. 2015

Natural Science and Discovery

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In this review content, it has been described the botanical and the chemical properties of turmeric (Curcuma longa), and its curcuminoid polyphenolic structures and antioxidant and anticarcinogenic influences on various cell proliferation and apoptosis. Besides it was emphasized the innovative anticarcinogen complex as boroncurcumin, and the safety evaluation with turmeric curcumin and the dose and toxicity in consuming for animals and human.

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Curcumin as a DNA Topoisomerase II Poison

Cited by 99 publications

References 32 publications

The dark side of curcumin

The dark side of curcumin

Cytotoxic activity of 4′-hydroxychalcone derivatives against Jurkat cells and their effects on mammalian DNA topoisomerase I

Turmeric Curcuminoid Polyphenolics as Antioxidant and Anticarcinogenic Agents

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