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

被引：28

作者：

Alauddin, Md ^{[1
]}

Okumura, Toshiyuki ^{[1
,2
]}

Rajaxavier, Janet ^{[1
]}

Khozooei, Shayan ^{[1
]}

Poeschel, Simone ^{[3
]}

Takeda, Satoru ^{[2
]}

Singh, Yogesh ^{[4
]}

Brucker, Sara Y. ^{[1
]}

Wallwiener, Diethelm ^{[1
]}

Koch, Andre ^{[1
]}

Salker, Madhuri S. ^{[1
]}

机构：

[1] Eberhard Karls Univ Tuebingen, Dept Womens Hlth, D-72076 Tubingen, Germany

[2] Juntendo Univ, Sch Med, Dept Obstet & Gynecol, Tokyo 1138421, Japan

[3] Eberhard Karls Univ Tuebingen, Image Stream Core Facil, D-72076 Tubingen, Germany

[4] Eberhard Karls Univ Tuebingen, Inst Med Genet & Appl Genom, D-72076 Tubingen, Germany

来源：

MOLECULAR NUTRITION & FOOD RESEARCH | 2020年 / 64卷 / 07期

关键词：

actin polymerization; carcinoma cells; PAK1; Rac1; FOCAL ADHESION KINASE; ELLAGIC ACID; BREAST-CANCER; TYROSINE PHOSPHORYLATION; MECHANICAL STIFFNESS; COLONIC METABOLITE; POMEGRANATE JUICE; CDC42; GTPASES; MICROBIOTA; RAC1;

D O I：

10.1002/mnfr.201900390

中图分类号：

TS2 [食品工业];

学科分类号：

0832 ;

摘要：

Scope Urolithin A (UA) is a gut-derived bacterial metabolite from ellagic acid found in pomegranates, berries, and nuts can downregulate cell proliferation and migration. Cell proliferation and cell motility require actin reorganization, which is under control of ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1). The present study explores whether UA can modify actin cytoskeleton in cancer cells. Methods The effect of UA on globular over filamentous actin ratio is determined utilizing Western blotting, immunofluorescence, and flow cytometry. Rac1 and PAK1 levels are measured by quantitative RT-PCR and immunoblotting. As a result, a 24 h treatment with UA (20 mu m) significantly decreased Rac1 and PAK1 transcript levels and activity, depolymerized actin and wound healing. The effect of UA on actin polymerization is mimicked by pharmacological inhibition of Rac1 and PAK1. The effect is also mirrored by knock down using siRNA. Conclusion UA leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization and migration. Thus, use of dietary UA in cancer prevention or as adjuvant therapy is promising.

引用

页数：11

共 60 条

[11] Identification of urolithin A as a metabolite produced by human colon microflora from ellagic acid and related compounds [J].

Cerdá, B ;

Periago, P ;

Espín, JC ;

Tomás-Barberán, FA .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2005, 53 (14) :5571-5576

[12]

Cortés-Martín A, 2018, FOOD FUNCT, V9, P4100, DOI [10.1039/c8fo00956b, 10.1039/C8FO00956B]

[13]

Cozza G., CHEM MED CHEM, V6, P2273

[14] pH sensing and regulation in cancer [J].

Damaghi, Mehdi ;

Wojtkowiak, Jonathan W. ;

Gillies, Robert J. .

FRONTIERS IN PHYSIOLOGY, 2013, 4

[15] Structural, Mechanical, and Dynamical Variability of the Actin Cortex in Living Cells [J].

Eghiaian, Frederic ;

Rigato, Annafrancesca ;

Scheuring, Simon .

BIOPHYSICAL JOURNAL, 2015, 108 (06) :1330-1340

[16] The gut microbiota and lipid metabolism: Implications for human health and coronary heart disease [J].

Fava, F. ;

Lovegrove, J. A. ;

Gitau, R. ;

Jackson, K. G. ;

Tuohy, K. M. .

CURRENT MEDICINAL CHEMISTRY, 2006, 13 (25) :3005-3021

[17] Cell mechanics and the cytoskeleton [J].

Fletcher, Daniel A. ;

Mullins, Dyche .

NATURE, 2010, 463 (7280) :485-492

[18] Analysis of turnover dynamics of the submembranous actin cortex [J].

Fritzsche, Marco ;

Lewalle, Alexandre ;

Duke, Tom ;

Kruse, Karsten ;

Charras, Guillaume .

MOLECULAR BIOLOGY OF THE CELL, 2013, 24 (06) :757-767

[19] Time Course Production of Urolithins from Ellagic Acid by Human Gut Microbiota [J].

Garcia-Villalba, Rocio ;

Beltran, David ;

Carlos Espin, Juan ;

Victoria Selma, Maria ;

Tomas-Barberan, Francisco A. .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2013, 61 (37) :8797-8806

[20] Signal Transduction in smooth muscle - Invited review: Focal adhesion and small heat shock proteins in the regulation of actin remodeling and contractility in smooth muscle [J].

Gerthoffer, WT ;

Gunst, SJ .

JOURNAL OF APPLIED PHYSIOLOGY, 2001, 91 (02) :963-972

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