Genistein inhibition of the growth of human breast cancer cells: Independence from estrogen receptors and the multi-drug resistance gene

Peterson, Greg; Barnes, Stephen

doi:10.1016/0006-291x(91)91423-a

Cited by 431 publications

(173 citation statements)

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“…A regular daily consumption of soy protein isolates (130 mg=day isoflavones) raises plasma concentrations of the isoflavones genistein and daidzein above the levels of the average Japanese male (Gooderham et al, 1996). Isoflavonoids inhibit tumour development and growth in cell lines (Peterson & Barnes, 1991. It is possible that any health benefit from soya products may be steroid independent (Nakhla et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

“…In vitro, isoflavonoids inhibit the enzymes 5a-reductase and 17b hydroxysteroid dehydrogenase (both of which are required for androgen synthesis; Evans et al, 1995;Mäkelä et al, 1998), inhibit angiogenesis, DNA topoisomerases and tyrosine-specific protein kinases (Markovits et al, 1989). Isoflavonoids inhibit tumour development and growth in cell lines (Peterson & Barnes, 1991 and in animal models (Mäkelä et al, 1995;Pollard & Luckert, 1997;Zhou et al, 1999). In Asian populations, prostatic carcinoma is less aggressive than in Western populations (Breslow et al, 1977) and the decreased incidence of the disease correlates with increased soya intake (Severson et al, 1989).…”

Section: Phytoestrogensmentioning

confidence: 99%

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Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men

et al. 2003

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Objective: We examined the effects on serum sex steroids, lipids and markers of oxidative stress of supplementing the diets of healthy male volunteers with scones made with soya flour. Design: A randomized placebo controlled cross-over trial. Setting: University Hospital of Wales. Subjects: Twenty volunteers recruited by advertisement. Interventions: Male volunteers ate three scones a day in addition to their normal diet for a period of 6 weeks. The scones were made with either wheat or soya flour (containing 120 mg=day of isoflavones). Blood was analysed for sex steroids (testosterone, dihydro-testosterone, oestradiol, oestrone, sex hormone binding globulin, albumin and the concentration of non-protein bound sex steroids were calculated), lipid profile (total cholesterol, high density lipoprotein cholesterol and triglycerides) and measures of oxidative stress (hydroperoxides, susceptibility of LDL to oxidation with copper and myeloperoxidase). Results: The volunteers' mean age was 35.6 (s.d. 11.2) y. Total serum testosterone fell in volunteers taking the soya scones (19.3 -18.2 nmol=l; 95% CI 1.01, 1.12; P ¼ 0.03). No significant changes were seen in the concentrations of the other serum sex steroids, albumin or sex hormone binding globulin throughout the study. Significant improvements in two of the three markers of oxidative stress were seen in volunteers taking soya scones. Lag time for myeloperoxidase rose from 55.0 to 68.0 min (95% CI 7 16.0, 7 3.5; P ¼ 0.009) and the presence of hydroperoxides decreased from 2.69 to 2.34 mmol=l (95% CI 0.12, 0.71; P ¼ 0.009). There were no changes seen in serum triglycerides or cholesterol. Conclusions: We have shown that soya supplements reduce serum testosterone and improve markers of oxidative stress. These findings provide a putative mechanism by which soya supplements could protect against prostatic disease and atherosclerosis. Further dietary studies with clinical end points are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Phytoestrogensmentioning

confidence: 99%

Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men

et al. 2003

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“…Daidzein and genistein but not their glucoside forms were absorbed from the stomach, and genistein was better absorbed than daidzein 1,19,22 . Genistein had been reported to have a higher antiproliferative effect on the growth of human breast carcinoma and prostate cancer cells compared to genistin 17,18 . All those reports indicated that the function of isoflavones increased during the fermentation, and fermented soybean foods with high contents of aglycones had the advantage of functional foods.…”

Section: Research On Traditional Fermented Soybean Foods In Chinamentioning

confidence: 99%

Function of Traditional Foods and Food Culture in China

Li-te¹,

Luo²,

Saito³

2004

JARQ

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“…The naturally-occurring plant isoflavone, genestein, became of interest in this regard, because of its dual effects of direct antitumour activities (mitotic arrest and apoptosis) and antiangiogenesis. [4][5][6][7][8][9][10][11][12] However, genistein has not been considered for development as a chemotherapeutic because of its poor bio-availability and high rate of metabolism, and the fact that the potencies of its anticancer actions are relatively modest.The experimental anticancer drug, phenoxodiol (PXD), is a sterically-modified version of genistein, which has substantially improved bio-availability and lower rate of metabolism and increased antitumour potency. PXD is currently undergoing Phase II clinical studies for the treatment of hormone-refractory prostatic adenocarcinoma, recurrent ovarian cancer, renal carcinoma and cervical squamous cell carcinoma.…”

mentioning

confidence: 99%

Phenoxodiol, an experimental anticancer drug, shows potent antiangiogenic properties in addition to its antitumour effects

Gamble

Xia

Hahn

et al. 2006

Intl Journal of Cancer

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Phenoxodiol (2H-1-benzopyran-7-0,1, 3-[4-hydroxyphenyl], PXD) is a synthetic analogue of the naturally-occurring plant isoflavone and anticancer agent, genistein. PXD directly induces mitotic arrest and apoptosis in most cancer cells and is currently undergoing clinical trials, as a chemotherapeutic in ovarian and prostate cancers. We show here that PXD also exhibits potent antiangiogenic properties. Thus, it inhibited endothelial cell proliferation, migration and capillary tube formation and inhibited expression of the matrix metalloproteinase MMP-2, a major matrix degrading enzyme. Importantly, we demonstrate that PXD is functional in vivo since it inhibited the extent of capillary tube invasion in an in vivo model of angiogenesis. We show that phenoxodiol inhibits hallmarks of endothelial cell activation, namely TNF or IL-1 induced E-selectin and VCAM-1 expression and IL-8 secretion. However, PXD had no effect on unstimulated endothelial cells. We also describe that PXD inhibits the lipid kinase sphingosine kinase, which recently has been implicated in endothelial cell activation and angiogenesis as well as oncogenesis. Thus, our results suggest that PXD may be an effective anticancer drug targeting the two drivers of tumour growth -the proliferation of the tumour cells themselves and the angiogenic and inflammatory stimulation of the vasculature. ' 2005 Wiley-Liss, Inc.Key words: flavonoids; cancer; angiogenesis; sphingosine kinase It is now well recognised that successful tumour growth involves uncontrolled proliferation of tumour cells and a supply of necessary nutrients delivered through a network of newly formed blood vessels. The ability of the tumour cells to stimulate angiogenesis is viewed as the ''angiogenic switch'' 1-3 a state essential for the continued growth and expansion of the tumour mass. Thus, combination therapy using drugs directed towards inhibition of the tumour cells, combined with drugs directed against the expanding vasculature is now considered a strategic direction for anticancer chemotherapy. The naturally-occurring plant isoflavone, genestein, became of interest in this regard, because of its dual effects of direct antitumour activities (mitotic arrest and apoptosis) and antiangiogenesis. [4][5][6][7][8][9][10][11][12] However, genistein has not been considered for development as a chemotherapeutic because of its poor bio-availability and high rate of metabolism, and the fact that the potencies of its anticancer actions are relatively modest.The experimental anticancer drug, phenoxodiol (PXD), is a sterically-modified version of genistein, which has substantially improved bio-availability and lower rate of metabolism and increased antitumour potency. PXD is currently undergoing Phase II clinical studies for the treatment of hormone-refractory prostatic adenocarcinoma, recurrent ovarian cancer, renal carcinoma and cervical squamous cell carcinoma. Two known biological effects of PXD are mitotic arrest of tumour cells in G1 of the cell cycle as a result of p53-independent upregula...

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Genistein inhibition of the growth of human breast cancer cells: Independence from estrogen receptors and the multi-drug resistance gene

Cited by 431 publications

References 15 publications

Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men

Dietary supplements of soya flour lower serum testosterone concentrations and improve markers of oxidative stress in men

Function of Traditional Foods and Food Culture in China

Phenoxodiol, an experimental anticancer drug, shows potent antiangiogenic properties in addition to its antitumour effects

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