Genistein—A dietary compound inducing hormonal and metabolic changes

Szkudelska, Katarzyna; Nogowski, Leszek

doi:10.1016/j.jsbmb.2007.01.005

Cited by 112 publications

(84 citation statements)

References 57 publications

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“…Additionally, genistein intake is also associated with altered expression of genes engaged in lipid metabolism and disturbed glucose transport into cells affecting lipolysis, lipogenesis and altered ATP synthesis. These metabolic and hormonal changes have been succinctly summarized by Szkudelska and Nogowski in a review article [14].…”

Section: Biological Effects Of Genisteinmentioning

confidence: 99%

Multi-targeted therapy of cancer by genistein

Banerjee¹,

Li²,

Wang³

et al. 2008

Cancer Letters

539

383

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Soy isoflavones have been identified as dietary components having an important role in reducing the incidence of breast and prostate cancers in Asian countries. Genistein, the predominant isoflavone found in soy products, has been shown to inhibit the carcinogenesis in animal models. There is a growing body of experimental evidence showing that the inhibition of human cancer cell growth by genisteinis mediated via the modulation of genes that are related to the control of cell cycle and apoptosis. It has been shown that genistein inhibits the activation of NF-κB and Akt signaling pathways, both of which are known to maintain a homeostatic balance between cell survival and apoptosis. Moreover, genistein antagonizes estrogen-and androgen-mediated signaling pathways in the processes of carcinogenesis. Furthermore, genistein has been found to have antioxidant properties, and shown to be a potent inhibitor of angiogenesis and metastasis. Taken together, both in vivo and in vitro studies have clearly shown that genistein, one of the major soy isoflavones, is a promising agent for cancer chemoprevention and further suggest that it could be an adjunct to cancer therapy by virtue of its effects on reversing radioresistance and chemoresistance. In this review, we attempt to provide evidence for these preventive and therapeutic effects of genistein in a succinct manner highlighting comprehensive state-of-the-art knowledge regarding its multi-targeted biological and molecular effects in cancer cells.

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Section: Biological Effects Of Genisteinmentioning

confidence: 99%

Multi-targeted therapy of cancer by genistein

Banerjee¹,

Li²,

Wang³

et al. 2008

Cancer Letters

539

383

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“…7 On the other hand, both genistein and rhodamine B are not specific inhibitors of GAG synthesis, and they have other biological functions. 8,9 Therefore, we aimed to develop a method for specific inhibition of GAG synthesis.…”

Section: Introductionmentioning

confidence: 99%

Impairment of glycosaminoglycan synthesis in mucopolysaccharidosis type IIIA cells by using siRNA: a potential therapeutic approach for Sanfilippo disease

2009

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Mucopolysaccharidoses (MPS) are severe inherited metabolic disorders from the group of lysosomal storage diseases. They are caused by deficiency in the activity of enzymes involved in the degradation of glycosaminoglycans (GAGs) and resultant accumulation of these compounds in the cells of patients. Although enzyme replacement therapy has become available for some MPS types (MPS I, MPS II and MPS VI), this treatment is not efficient when neurological symptoms occur, especially in MPS III (Sanfilippo disease). Recent studies indicated that substrate reduction therapy (SRT) may be an effective option for the treatment of neurodegenerative lysosomal storage diseases, including MPS III. However, previous attempts to SRT for MPS III focused on the use of non-specific inhibitors of GAG synthesis. Thus, we aimed to use the small interfering RNA (siRNA) procedure to control expression of particular genes, whose products are involved in GAG synthesis. In this report we show that, in MPS IIIA fibroblasts, we were able to reduce mRNA levels of four genes, XYLT1, XYLT2, GALTI and GALTII, whose products are involved in GAG synthesis. This decrease in levels of transcripts corresponded to a decrease in levels of proteins encoded by them. Moreover, efficiency of GAG production in these fibroblasts was considerably reduced after treatment of the cells with siRNA. These results indicate that efficient reduction of GAG synthesis may be achieved by the use of siRNA.

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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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Genistein—A dietary compound inducing hormonal and metabolic changes

Cited by 112 publications

References 57 publications

Multi-targeted therapy of cancer by genistein

Multi-targeted therapy of cancer by genistein

Impairment of glycosaminoglycan synthesis in mucopolysaccharidosis type IIIA cells by using siRNA: a potential therapeutic approach for Sanfilippo disease

Gene expression‐targeted isoflavone therapy

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