Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells

Norden, Elisabeth; Heiß, Elke H.

doi:10.1093/carcin/bgy158

Cited by 43 publications

(38 citation statements)

References 51 publications

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“…More recent evidence[ 28 ] showing a dose-dependent anti-clonogenic effect of long-term exposure to UA in CRC cell lines, indicates that a decrease in the colony formation is exerted through the senescence induction via the p53/p21 pathway, rather than by cell cycle arrest or apoptosis, which required much higher concentrations[ 28 ]. These data are consistent with previous results[ 32 ], also suggesting that the antiproliferative effect of long-term exposure to UA in a colon cancer cell line was mediated through the p53/p21-dependent senescence-like growth arrest. This action was synergistic with the standard chemotherapeutic drug oxaliplatin[ 32 ].…”

Section: Intestinesupporting

confidence: 93%

“…These data are consistent with previous results[ 32 ], also suggesting that the antiproliferative effect of long-term exposure to UA in a colon cancer cell line was mediated through the p53/p21-dependent senescence-like growth arrest. This action was synergistic with the standard chemotherapeutic drug oxaliplatin[ 32 ]. González-Sarrías et al[ 33 ] have also demonstrated that UA at concentrations achievable in the human colorectum, can potentiate the anticancer effects of 5-fluorouracil (5-FU) on human colon cancer cells.…”

Section: Intestinesupporting

confidence: 93%

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Potential of the ellagic acid-derived gut microbiota metabolite – Urolithin A in gastrointestinal protection

Kujawska

Jodynis‐Liebert

2020

WJG

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Urolithin A (UA) is a metabolic compound generated during the biotransformation of ellagitannins by the intestinal bacteria. The physiologically relevant micromolar concentrations of UA, achieved in the plasma and gastrointestinal tract (GI) after consumption of its dietary precursors, have been revealed to offer GI protection. The health benefit has been demonstrated to be principally related to anticancer and anti-inflammatory effects. UA has been shown to possess the capability to regulate multiple tumor and inflammatory signaling pathways and to modulate enzyme activity, including those involved in carcinogen biotransformation and antioxidant defense. The purpose of this review is to gather evidence from both in vitro and in vivo studies showing the potential of UA in GI protection alongside suggested mechanisms by which UA can protect against cancer and inflammatory diseases of the digestive tract. The data presented herein, covering both studies on the pure compound and in vivo generated UA form its natural precursor, support the potential of this metabolite in treatment interventions against GI ailments.

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Section: Intestinesupporting

confidence: 93%

Section: Intestinesupporting

confidence: 93%

Potential of the ellagic acid-derived gut microbiota metabolite – Urolithin A in gastrointestinal protection

Kujawska

Jodynis‐Liebert

2020

WJG

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“…Norden and Heiss also reported that urolithin A-induced p53 stabilization in HCT-116 cells not only exerted antiproliferative effects (IC 50 = 19 μ M) but also synergized with the anticancer drug oxaliplatin. In the absence of p53, a significant decrease in urolithin A antiproliferative activity was however noted (IC 50 = 38 μ M) [ 80 ].…”

Section: Urolithin Activity In the Modulation Of Oxidative Stressmentioning

confidence: 99%

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

Djedjibegović

Marjanović

Panieri³

et al. 2020

Oxidative Medicine and Cellular Longevity

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Oxidative stress is a state of excess of prooxidative species relative to the antioxidant defenses (enzymatic and nonenzymatic) in a living organism. The consequence of this imbalance is damage of the major cellular macromolecules (carbohydrates, lipids, proteins, and DNA), which further leads to a gradual loss of tissue and organ function. It has been shown that oxidative stress plays an important role in the pathogenesis of many chronic diseases (cardiovascular, metabolic, and neurodegenerative diseases and cancer) and in the process of aging. Thus, many strategies to combat oxidative stress have been proposed and tested. In this context, food rich in antioxidants has received great attention. Pomegranate, berries, and walnuts have been recognized as “superfood” particularly for their cardioprotective effects. The common characteristic of these foods is the high content of ellagitannins. Since tannins are not bioavailable, they have been neglected in nutrition science and even considered antinutrients for a long time. However, this view has changed dramatically once it was recognized that ellagic acid, released from ellagitannins in the gastrointestinal system, is further metabolized by colonic microbiota to bioavailable compounds—known as urolithins. Thus, urolithins (3,4-benzocoumarin derivatives) have emerged as novel natural bioactive compounds and are now the focus of extensive investigations. So far, urolithins were shown to be powerful modulators of oxidative stress and agents with potential anti-inflammatory, antiproliferative, and antiaging properties. Furthermore, a few synthetic derivatives of urolithins were recognized as lead compounds for new drug development. Available data on urolithin synthesis, physicochemical and pharmacokinetic characteristics, biological activity, and safety will be presented in this review.

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“…Nevertheless, EA is poorly absorbed and quickly eliminated, and the biological activity of EA is controversial. Interestingly, recent published studies have described the biological effects of UA, including anti-proliferation in cancer, antiinflammation, anti-oxidant activity, improved lipid metabolism [13][14][15]. UA inhibits the catabolic effect of TNF-α on nucleus pulposus cells and alleviates intervertebral disc degeneration in vivo [16].…”

Section: Introductionmentioning

confidence: 99%

Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes

et al. 2020

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Background: Osteoarthritis (OA) is characterized by inflammation and extracellular matrix (ECM) degradation and is one of the most common chronic degenerative joint diseases that causes pain and disability in adults. Urolithin A (UA) has been widely reported for its anti-inflammatory properties in several chronic diseases. However, the effects of UA on OA remain unclear. The aim of the current study was to investigate the anti-inflammatory effects and mechanism of UA in interleukin-1β (IL-1β)-induced chondrocytes. Results: No marked UA cytotoxicity was noted, and UA protected cartilage from damage following IL-1β stimulation in micromasses. Moreover, UA promoted the expression of anabolic factors including Sox-9, Collagen II, and Aggrecan while inhibiting the expression of catabolic factors such as matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) in rat chondrocytes. Protective effects of UA were also observed in ex vivo organ culture of articular cartilage. Mechanistically, IL-1β significantly activated and upregulated the expression of pERK 1/2, p-JNK, p-P38, and p-P65, while UA protected chondrocytes against IL-1β-induced injury by activating the mitogen-activated kinase (MAPK)/nuclear factor-κB (NF-κB) signaling pathways. Conclusion: Our results provide the evidence that UA could attenuate IL-1β-induced cell injury in chondrocytes via its anti-inflammatory action. UA may be a promising therapeutic agent in the treatment of OA.

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Urolithin A gains in antiproliferative capacity by reducing the glycolytic potential via the p53/TIGAR axis in colon cancer cells

Abstract: Urolithin A inhibits growth of colon cancer cells alone and synergistically in combination with oxaliplatin. Those activities are markedly supported by activation of the p53/TIGAR axis and subsequent reduction of the cellular glycolytic potential by urolithin A.

Cited by 43 publications

References 51 publications

Potential of the ellagic acid-derived gut microbiota metabolite – Urolithin A in gastrointestinal protection

Potential of the ellagic acid-derived gut microbiota metabolite – Urolithin A in gastrointestinal protection

Ellagic Acid-Derived Urolithins as Modulators of Oxidative Stress

Urolithin a attenuates IL-1β-induced inflammatory responses and cartilage degradation via inhibiting the MAPK/NF-κB signaling pathways in rat articular chondrocytes

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