Gut Bacterial Metabolite Urolithin A Decreases Actin Polymerization and Migration in Cancer Cells

Alauddin,; Okumura, Toshiyuki; Rajaxavier, Janet; Khozooei, Shayan; Pöschel, Simone; Takeda, Satoru; Singh, Yogesh; Brucker, Sara Y.; Wallwiener, D.; Koch, Andrè; Salker, Madhuri S.

doi:10.1002/mnfr.201900390

Cited by 26 publications

(24 citation statements)

References 60 publications

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“…Tables 2 and 4 are most interesting, as CH redifferentiation or prevention of CH dedifferentiation would require prevention of actin polymerization or enhancement of actin depolymerization. Actin inhibitors (Table 2), such as chaetoglobosin A and J [362,363], cytochalasin B and D [364,365], latrunculin A and B [366,367], and urolithin A, which was only recently shown to decrease actin polymerization [368], have already been evaluated in clinical trials. Some ROCK inhibitors (Table 4) have also been tested in all clinical trial phases for the treatment of glaucoma and ocular hypertension [369] and could play a role in the treatment of acute lung injury [370].…”

Section: Discussionmentioning

confidence: 99%

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function

Lauer

Selig

Hart

et al. 2021

IJMS

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Numerous studies have assembled a complex picture, in which extracellular stimuli and intracellular signaling pathways modulate the chondrocyte phenotype. Because many diseases are mechanobiology-related, this review asked to what extent phenotype regulators control chondrocyte function through the cytoskeleton and cytoskeleton-regulating signaling processes. Such information would generate leverage for advanced articular cartilage repair. Serial passaging, pro-inflammatory cytokine signaling (TNF-α, IL-1α, IL-1β, IL-6, and IL-8), growth factors (TGF-α), and osteoarthritis not only induce dedifferentiation but also converge on RhoA/ROCK/Rac1/mDia1/mDia2/Cdc42 to promote actin polymerization/crosslinking for stress fiber (SF) formation. SF formation takes center stage in phenotype control, as both SF formation and SOX9 phosphorylation for COL2 expression are ROCK activity-dependent. Explaining how it is molecularly possible that dedifferentiation induces low COL2 expression but high SF formation, this review theorized that, in chondrocyte SOX9, phosphorylation by ROCK might effectively be sidelined in favor of other SF-promoting ROCK substrates, based on a differential ROCK affinity. In turn, actin depolymerization for redifferentiation would “free-up” ROCK to increase COL2 expression. Moreover, the actin cytoskeleton regulates COL1 expression, modulates COL2/aggrecan fragment generation, and mediates a fibrogenic/catabolic expression profile, highlighting that actin dynamics-regulating processes decisively control the chondrocyte phenotype. This suggests modulating the balance between actin polymerization/depolymerization for therapeutically controlling the chondrocyte phenotype.

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Section: Discussionmentioning

confidence: 99%

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function

Lauer

Selig

Hart

et al. 2021

IJMS

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“…The most mature mechanism of Rac1 mediated cytoskeletal recombination is through PAKs (P21 activated kinase) (32). Both cell proliferation and cell movement require actin recombination, which is controlled by Rac1 and PAK1 (31). PAKs can be divided into two groups: one is PAK 1-3 and the other group is PAK 4-6 (33).…”

Section: Rac1 Regulates Cell Adhesion Morphology and Movementmentioning

confidence: 99%

Rac1, A Potential Target for Tumor Therapy

et al. 2021

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RAS-related C3 botulinum toxin substrate 1 (Rac.1) is one of the important members of Rho GTPases. It is well known that Rac1 is a cytoskeleton regulation protein that regulates cell adhesion, morphology, and movement. Rac1 is highly expressed in different types of tumors, which is related to poor prognosis. Studies have shown that Rac1 not only participates in the tumor cell cycle, apoptosis, proliferation, invasion, migration and angiogenesis, but also participates in the regulation of tumor stem cell, thus promoting the occurrence of tumors. Rac1 also plays a key role in anti-tumor therapy and participates in immune escape mediated by the tumor microenvironment. In addition, the good prospects of Rac1 inhibitors in cancer prevention and treatment are exciting. Therefore, Rac1 is considered as a potential target for the prevention and treatment of cancer. The necessity and importance of Rac1 are obvious, but it still needs further study.

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“…The study showed Urolithin-A inhibited cell motility as well. 50) A lot of studies demonstrated that Urolithin-A induced cell cycle arrest and apoptosis in various type of cancer. Cell cycle regulation and apoptosis regulation are intimately connected each other.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, wound healing assay showed that Urolithin-A inhibited cell motility in Ishikawa cell. 50) Urolithin-A inhibited cell motility by regulating Akt pathway in human pancreatic cancer cell line, BxPC3, MiaPaCa2 and PANC1. 43)…”

Section: Urolithin-a Inhibits Cancer Metastasismentioning

confidence: 99%

The Potential as New Treatment Agent of Urolithin-A Metabolized from Ellagic Acid by Gut Microbiota in Cancer

Okumura

2021

Juntendo Medical Journal

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Cancer is the leading cause of death in Japan. Cancer is treated by multidisciplinary therapy such as surgery, chemotherapy, molecular target therapy and radiotherapy. However, almost of advanced cancer relapse after treatment. The relapsed cancer acquires resistance to the therapeutic agents we already used. The prognosis of relapsed cancer is very poor. Therefore, new treatment agents are needed urgently. In recent years metabolites derived from natural foods are focused as new therapeutic agents of cancer diseases. The metabolites are expected to cause less side effect than chemotherapy and have same effect as chemotherapy to cancer. Furthermore therapeutic agents from natural foods are Ellagic acid is metabolite derived from nuts, berries, and pomegranates.Ellagic acid is known to have anticancer effects, due to affecting apoptosis, cell proliferation and cell cycle regulation. Some of metabolites from ellagic acid also have anticancer effect. Urolithins are gut derived bacterial metabolites from ellagic acid. Many articles reported that Urolithin-A has anticancer effect for many cancers.Urolithin-A was reported to regulate p53 protein, caspase 3, caspase 7, AKT, aromatase and PARP in some cancers. Actin polymerization is regulated via Rac1 pathway by Urolithin-A in endometrial cancer. Furthermore, proliferation of many cancer cell lines is suppressed by UA. Safety of UA was investigated by using Rat model. The article suggested Urolithin-A has less genotoxicity compared with cyclophosphamide. Thus, Urolithin-A might be able to have a role as new treatment agent to cancer.

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Gut Bacterial Metabolite Urolithin A Decreases Actin Polymerization and Migration in Cancer Cells

Cited by 26 publications

References 60 publications

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function

Articular Chondrocyte Phenotype Regulation through the Cytoskeleton and the Signaling Processes That Originate from or Converge on the Cytoskeleton: Towards a Novel Understanding of the Intersection between Actin Dynamics and Chondrogenic Function

Rac1, A Potential Target for Tumor Therapy

The Potential as New Treatment Agent of Urolithin-A Metabolized from Ellagic Acid by Gut Microbiota in Cancer

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