Genistein: a natural isoflavone with a potential for treatment of genetic diseases

Węgrzyn, Grzegorz; Jakóbkiewicz‐Banecka, Joanna; Gabig-Cimińska, Magdalena; Piotrowska, Ewa; Narajczyk, Magdalena; Kłoska, Anna; Malinowska, Marcelina; Dziedzic, Dariusz; Gołębiewska, Izabela; Moskot, Marta; Węgrzyn, Alicja

doi:10.1042/bst0380695

Cited by 52 publications

(45 citation statements)

References 48 publications

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“…Among many varied applications, genistein has been demonstrated previously to reduce the efficiency of glycosaminoglycan synthesis, leading to its reduced accumulation in MPS cells (7,23,24). It was assumed that genistein may impair GAG metabolism by affecting expression of certain genes; therefore, comprehensive transcriptomic studies, so far not reported in the literature, were strongly desired.…”

Section: Discussionmentioning

confidence: 99%

The Phytoestrogen Genistein Modulates Lysosomal Metabolism and Transcription Factor EB (TFEB) Activation

Moskot

Montefusco

Jakóbkiewicz‐Banecka

et al. 2014

Journal of Biological Chemistry

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116

113

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Background: Genistein is a potential drug for certain inherited lysosomal disorders. Results: Genistein influences molecular cross-talk in the cell responsible for lysosomal enhancement. Conclusion: Genistein potentiates lysosomal metabolism by activating transcription factor EB (TFEB).Significance: The explanation of genistein action offers more adequate therapeutic procedures for the treatment of some lysosomal storage diseases.

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Section: Discussionmentioning

confidence: 99%

The Phytoestrogen Genistein Modulates Lysosomal Metabolism and Transcription Factor EB (TFEB) Activation

Moskot

Montefusco

Jakóbkiewicz‐Banecka

et al. 2014

Journal of Biological Chemistry

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116

113

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“…This question is substantiated especially in the light of various biological activities of genistein, described previously (for reviews see refs. [39][40][41]. Moreover, results of recent studies on pathomechanisms of MPS led to proposals that not only primary GAG storage but also secondary reactions are crucial for development of symptoms characteristic for this disease.…”

Section: Secondary Roles Of Genistein In Treatment Of Mpsmentioning

confidence: 99%

Gene expression‐targeted isoflavone therapy

Węgrzyn

2012

IUBMB Life

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SummaryLysosomal storage diseases (LSD) form a group of inherited metabolic disorders caused by dysfunction of one of the lysosomal proteins, resulting in the accumulation of certain compounds. Although these disorders are among first genetic diseases for which specific treatments were proposed, there are still serious unsolved problems that require development of novel therapeutic procedures. An example is neuronopathy, which develops in most of LSD and cannot be treated efficiently by currently approved therapies. Recently, a new potential therapy, called gene expression-targeted isoflavone therapy (GET IT), has been proposed for a group of LSD named mucopolysaccharidoses (MPS), in which storage of incompletely degraded glycosaminoglycans (GAGs) results in severe symptoms of virtually all tissues and organs, including central nervous system. The idea of this therapy is to inhibit synthesis of GAGs by modulating expression of genes coding for enzymes involved in synthesis of these compounds. Such a modulation is possible by using isoflavones, particularly genistein, which interfere with a signal transduction process necessary for stimulation of expression of certain genes. Results of in vitro experiments and studies on animal models indicated a high efficiency of GET IT, including correction of behavior of affected mice. However, clinical trials, performed with soy isoflavone extracts, revealed only limited efficacy. This caused a controversy about GET IT as a potential, effective treatment of patients suffering from MPS, especially neuronopathic forms of these diseases. It this critical review, I present possible molecular mechanisms of therapeutic action of isoflavones (particularly genistein) and suggest that efficacy of GET IT might be sufficiently high when using relatively high doses of synthetic genistein (which was employed in experiments on cell cultures and mouse models) rather than low doses of soy isoflavone extracts (which were used in clinical trials). This proposal can be tested in double-blinded, placebo-controlled clinical trials.2012 IUBMB IUBMB Life, 64(4): [307][308][309][310][311][312][313][314][315] 2012

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“…MPS are caused by the absence or malfunction of lysosomal enzymes needed to break down HS, CS, DS, KS, or HA GAGs [15] that leads to GAG accumulation in lysosomes in virtually all cells of the affected organism. It causes a progressive damage of tissues leading to severe dysfunctions of various organs, including the heart, bones, respiratory system, joints, and central nervous system (CNS), with an average expected lifespan of one or two decades [13,14,[16][17][18][19]. Depending on the lacking or deficient enzyme associated with the accumulated GAGs, 11 types and subtypes of MPS have been recognized [13,16,[18][19][20][21][22][23].…”

Section: Genistein Enhances or Reduces Glycosaminoglycan Quantity In mentioning

confidence: 99%

“…The mucopolysaccharidoses (MPSs) are part of the lysosomal storage disease family, a group of more than 40 genetic disorders that result when the lysosome organelle in animal cells malfunctions [13,14]. MPS are caused by the absence or malfunction of lysosomal enzymes needed to break down HS, CS, DS, KS, or HA GAGs [15] that leads to GAG accumulation in lysosomes in virtually all cells of the affected organism.…”

Section: Genistein Enhances or Reduces Glycosaminoglycan Quantity In mentioning

confidence: 99%

Genistein Enhances or Reduces Glycosaminoglycan Quantity in a Cell Type-Specific Manner

Lan

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Genistein is a natural isoflavone enriched in soybeans. It has beneficial effects for patients with mucopolysaccharidose type III through inhibiting glycosaminoglycan biosynthesis. However, other studies indicate that genistein does not always inhibit glycosaminoglycan biosynthesis. Methods: To understand the underlying molecular mechanisms, CHOK1, CHO3.1, CHO3.3, and HCT116 cells were treated with genistein and the monosaccharide compositions and quantity of all glycans from the cell lysate were measured after thorough acid hydrolysis followed by HPLC analysis. In addition, the glycosaminoglycan disaccharide compositions were obtained by stable isotope labeling coupled with LC/MS analysis. Results: Genistein treatment reduced the amount of glycans but increased the amount of glycosaminoglycans in HCT116 cells. In contrast, genistein treatment reduced both glycan and glycosaminoglycan quantities in CHOK1, CHO3.1, and CHO3.3 cells in addition to differential changes in glycosaminoglycan disaccharide compositions. Conclusion: Genistein treatment reduced overall glycan quantity but glycosaminoglycan quantities were either increased or decreased in a cell type-dependent manner.

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Genistein: a natural isoflavone with a potential for treatment of genetic diseases

Cited by 52 publications

References 48 publications

The Phytoestrogen Genistein Modulates Lysosomal Metabolism and Transcription Factor EB (TFEB) Activation

The Phytoestrogen Genistein Modulates Lysosomal Metabolism and Transcription Factor EB (TFEB) Activation

Gene expression‐targeted isoflavone therapy

Genistein Enhances or Reduces Glycosaminoglycan Quantity in a Cell Type-Specific Manner

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