Effects of genistein and structurally related phytoestrogens on cell cycle kinetics and apoptosis in MDA-MB-468 human breast cancer cells.

Balabhadrapathruni, Srivani; Yurkow, Edward J.; Amenta, Peter S.; Thomas, Thresia

doi:10.3892/or.7.1.3

Cited by 56 publications

(68 citation statements)

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“…Similar to human cell line data, we found that the increased Bax/Bcl-2 ratio in the GL-1 cells (and 17-71 cells to a lesser extent) was due to an increase in proapoptotic Bax protein expression rather than a decrease in antiapoptotic Bcl-2 protein expression (23,40). Other cellular processes suggested to be involved in genistein-induced apoptosis include increased poly(ADP-ribose)polymerse cleavage (45), induced expression of p21 protein (46), and increased p53 phosphorylation (47). Further studies using these canine cells are needed to begin to mechanistically understand genisteininduced apoptosis.…”

Section: Discussionsupporting

confidence: 69%

Soy-Derived Isoflavones Inhibit the Growth of Canine Lymphoid Cell Lines

Jamadar-Shroff¹,

Papich²,

Suter³

2009

Clinical Cancer Research

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Purpose: This study aimed to evaluate the in vitro effects of genistein, both pure genistein and a commercially available form of genistein called Genistein Combined Polysacharride (GCP), against two canine B-cell lymphoid cell lines and determine the oral bioavailability of GCP when fed to normal dogs. Experimental Design: The in vitro effect of genistein and GCP was evaluated using cell proliferation and apoptotic assays. The IC 50 of both compounds was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay and propidium idodide staining. Apoptosis was evaluated using Annexin V staining, caspase 3 and 9 staining, and DNA laddering. Cell cycle analysis and Bcl-2/Bax ratios were also examined. An initial dose escalating pharmacokinetic study was used to determine if therapeutic serum levels of genistein could be reached with oral dosing of GCP in normal dogs. Results:The 72-hour in vitro IC 50 of genistein and GCP against the GL-1and17-71cells were both 10 Ag/mL and 20 Ag/mL, respectively. GCP led to cell death in both cell lines via apoptosis and treated cells exhibited increased Bax:Bcl-2 ratios. The serum concentrations of genistein in normal dogs given increasing oral doses of GCP did not reach the 72-hour in vitro IC 50 in a dose escalation study. Conclusions:The results of these studies support the notion that canine high-grade B-cell lymphoma may represent a relevant large animal model of human non-Hodgkin's lymphoma to investigate the utility of GCP in chemopreventive and/or treatment strategies that may serve as a prelude to human clinical lymphoma trials.

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Section: Discussionsupporting

confidence: 69%

Soy-Derived Isoflavones Inhibit the Growth of Canine Lymphoid Cell Lines

Jamadar-Shroff¹,

Papich²,

Suter³

2009

Clinical Cancer Research

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“…However, similar to quercetin, genistein is also known as a protein kinase inhibitor [39] and a ligand for type II EBS with subsequent inhibitory effect on cell proliferation [11]. Up to now, however, no differences in efficiency of kinase activity inhibition or type II EBSmediated inhibition of cell proliferation between quercetin and genistein have been reported that might account for the differences in effects seen [36,40].…”

Section: Discussionmentioning

confidence: 91%

“…Different mechanisms underlying the inhibition of cell proliferation by quercetin have been proposed, including DNA strand breakage [35], cell cycle arrest [36], and/or the induction of apoptosis [6,36], possibly by influencing the activity of various kinases, including phosphatidylinositol-3-kinase, tyrosine protein kinase and protein kinase C [33,34]. Another plausible mechanism of inhibition of cell proliferation, which is also in line with the estrogenic character of quercetin, is the interaction of quercetin with so-called type II estrogen binding sites (EBS) [37,38], probably involved in the inhibition of estrogen-stimulated growth in vivo [38].…”

Section: Discussionmentioning

confidence: 99%

The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor

Woude¹,

Veld

Jacobs

et al. 2005

Mol. Nutr. Food Res.

124

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Quercetin causes biphasic modulation of the proliferation of specific colon and mammary cancer cells. In this study, the possible involvement of the estrogen receptor (ER) in the stimulation of cell proliferation by quercetin was investigated. For this purpose, the effect of quercetin on cell proliferation was tested in ER-positive MCF-7 and T47D cells, and in ER-negative HCC-38 and MDA-MB231 cells. Quercetin stimulated proliferation of ER-positive cells only, suggesting this effect to be ER-dependent. In support of these results, quercetin induced ER-ERE-mediated gene expression in a reporter gene assay using U2-OS cells transfected with either ERalpha or ERbeta, with 10(5)-10(6) times lower affinity than 17beta-estradiol (E2) and 10(2)-10(3 )times lower affinity than genistein. Quercetin activated the ERbeta to a 4.5-fold higher level than E2, whereas the maximum induction level of ERalpha by quercetin was only 1.7 fold that of E2. These results point at the relatively high capacity of quercetin to stimulate supposed 'beneficial' ERbeta responses as compared to the stimulation of ERalpha, the receptor possibly involved in adverse cell proliferative effects. Altogether, the results of this study reveal that physiologically relevant concentrations of quercetin can exert phytoestrogen-like activity similar to that observed for the isoflavonoid genistein.

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“…These are overexpressed in cancer cells thereby conferring cancer cell protection against a variety of proapoptotic stimuli by functionally regulating signal transduction pathways associated with malignancy [60,61]. Structurally, the IAPs are similar with one or more 70 -80 amino acid baculovirus IAP repeat (BIR) domains with the core domain consiting of the variable sequence C(X) 2 C(X) 6 W(X) 3 D(X) 5 H(X) 6 C with the X representing any amino acid [46].…”

Section: Inhibitors Of Apoptosis Proteins (Iap)mentioning

confidence: 99%

Breast cancer: Small molecules targeting apoptosis, a prospective approach to safe scientific success

Choene¹,

Mthembu²,

Dlamini³

et al. 2012

ABB

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Breast carcinoma represents the second leading cause of cancer death in developed countries amongst women. Current cytotoxic chemotherapy plays an important role in the management of patients with hormone-insensitive or metastatic breast carcinoma, although most of them ultimately develop recurrences. Therefore, there is a need for novel targets and treatment strategies in patients with advanced breast carcinoma that is refractory to conventional chemotherapy. This paper summarizes current knowledge on breast cancer targets and molecular mechanisms that follows apoptosis induction.

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Effects of genistein and structurally related phytoestrogens on cell cycle kinetics and apoptosis in MDA-MB-468 human breast cancer cells.

Cited by 56 publications

References 0 publications

Soy-Derived Isoflavones Inhibit the Growth of Canine Lymphoid Cell Lines

Soy-Derived Isoflavones Inhibit the Growth of Canine Lymphoid Cell Lines

The stimulation of cell proliferation by quercetin is mediated by the estrogen receptor

Breast cancer: Small molecules targeting apoptosis, a prospective approach to safe scientific success

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