Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer

Rhodes, Lyndsay V.; Tilghman, Syreeta L.; Boué, Stephen M.; Wang, Shuchun; Khalili, Hafez; Muir, Shannon E.; Bratton, Melyssa R.; Zhang, Qiang; Wang, Guangdi; Burow, Matthew E.; Collins‐Burow, Bridgette M.

doi:10.3892/ol.2011.460

Cited by 48 publications

(40 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, these effects of Gly on insulin signaling are independent of classical ER-mediated effects (Boue et al 2012), and were found to work via the CaMKK-AMPK pathway in one study (Yoon et al 2013). Other non-ER-mediated mechanisms of Gly action have been found: Gly suppresses tumorigenesis in a xenografted triple-negative breast cancer cell line that lacks ERs (Rhodes et al 2012), inhibits lipid peroxidation in tissue extracts of rat brain, kidney and liver (Kim et al 2010b), upregulates expression of genes involved in lipid metabolism (Wood et al 2012), and inhibits p70S6-mediated phosphorylation of ERα (Bratton et al 2015). Collectively, these findings indicate that Gly may have multiple, context-dependent mechanisms of action, that E2 signaling is not the only target of Gly activity, and that in some cases E2 signaling is indirectly modified by Gly.…”

Section: Introductionmentioning

confidence: 99%

Soy glyceollins regulate transcript abundance in the female mouse brain

Bamji

Page

Patel

et al. 2015

Funct Integr Genomics

Self Cite

View full text Add to dashboard Cite

Glyceollins (Gly), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Gly exhibits mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Gly on gene expression in the brain are unknown. For this study, we implanted 17-β estradiol (E2) or placebo slow-release pellets into ovariectomized CFW mice followed by 11 days of exposure to Gly or vehicle i.p. injections. We then performed a microarray on total RNA extracted from whole brain hemispheres and identified differentially expressed genes (DEGs) by a 2 × 2 factorial ANOVA with an FDR = 0.20. In total, we identified 33 DEGs with a significant E2 main effect, 5 DEGs with a significant Gly main effect, 74 DEGs with significant Gly and E2 main effects (but no significant interaction term), and 167 DEGs with significant interaction terms. Clustering across all DEGs revealed that transcript abundances were similar between the E2+Gly and E2-only treatments. However, gene expression after Gly-only treatment was distinct from both of these treatments and was generally characterized by higher transcript abundance. Collectively, our results suggest that whether Gly acts in the brain through ER-dependent or ER-independent mechanisms depends on the target gene.

show abstract

Section: Introductionmentioning

confidence: 99%

Soy glyceollins regulate transcript abundance in the female mouse brain

Bamji

Page

Patel

et al. 2015

Funct Integr Genomics

Self Cite

View full text Add to dashboard Cite

show abstract

“…11 Among the biological effects of glyceollins are potential human health benefits including anti-fungal, anti-oxidant, anti-inflammatory, anti-diabetic, and cancer cell anti-proliferative activity along with other beneficial properties. 12,13,14 Recently, many studies have proposed glyceollins as prevention or therapy candidates for breast, ovarian, and prostate cancers. All three glyceollin isomers have exhibited anti-estrogenic effects on estrogen receptor function and estrogen-dependent tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Screening and Identification of Glyceollins and Their Metabolites by Electrospray Ionization Tandem Mass Spectrometry with Precursor Ion Scanning

et al. 2013

View full text Add to dashboard Cite

A method has been developed for screening glyceollins and their metabolites based upon precursor ion scanning. Under higher-energy collision conditions employing a triple quadrupole mass spectrometer in the negative ion mode, deprotonated glyceollin precursors yield a diagnostic radical product ion at m/z 148. We propose this resonance-stabilized radical anion, formed in violation of the even-electron rule, to be diagnostic of glyceollins and glyceollin metabolites. Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) established that scanning for precursors of m/z 148 can identify glyceollins and their metabolites from plasma samples originating from rats dosed with glyceollins. Precursor peaks of interest were found at m/z 337, 353, 355, 417, and 433. The peak at m/z 337 corresponds to deprotonated glyceollins, whereas the others represent metabolites of glyceollins. Accurate mass measurement confirmed m/z 417 to be a sulfated metabolite of glyceollins. The peak at m/z 433 is also sulfated, but it contains an additional oxygen, as confirmed by accurate mass measurement. The latter metabolite differs from the former likely by the replacement of a hydrogen with a hydroxyl moiety. The peaks at m/z 353 and 355 are proposed to correspond to hydroxylated metabolites of glyceollins wherein the latter additionally undergoes a double bond reduction.

show abstract

“…To investigate the ER-independent antiproliferative mechanism of glyceollin, we performed xenograft studies using triple negative breast cancer cells (MDA-MB231 and MDA-MB468 cells). Interestingly, our results demonstrated that glyceollin treatment caused a modest reduction in tumorigenesis in both cell lines, 61 a result of alterations in the miRnome and proteomic expression profile. Specifically, glyceollin-treated MDA-MB231 cells demonstrated a significant increase in miRNAs involved in EMT (miR-22, miR-29b, miR-29c, miR-30d, miR-34a and miR-195) and tumor suppressors (miR-181c and miR-181d).…”

Section: The Effect Of Glyceollins On Mirnamentioning

confidence: 64%

Phytoalexins, miRNAs and Breast Cancer: A Review of Phytochemical-mediated miRNA Regulation in Breast Cancer

Tilghman¹,

Rhodes²,

Bratton³

et al. 2013

hpu

Self Cite

View full text Add to dashboard Cite

There is growing interest in the diverse signaling pathways that regulate and affect breast tumorigenesis, including the role of phytochemicals and the emerging role of microRNAs (miRNAs). Recent studies demonstrate that miRNAs regulate fundamental cellular and developmental processes at the transcriptional and translational level under normal and disease conditions. While there is growing evidence to support the role of phytoalexin-mediated miRNA regulation of cancer, few reports address this role in breast cancer. Recent reports by our group and others demonstrate that natural products, including stilbenes, curcumin, and glyceollins, could alter the expression of specific miRNAs, which may lead to increased sensitivity of cancer cells to conventional anti-cancer agents and, therefore, hormone-dependent and hormone-independent tumor growth inhibition. This review will discuss how dietary intake of natural products, by regulating specific miRNAs, contribute to the prevention and treatment of breast cancer.

show abstract

Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer

Cited by 48 publications

References 74 publications

Soy glyceollins regulate transcript abundance in the female mouse brain

Soy glyceollins regulate transcript abundance in the female mouse brain

Screening and Identification of Glyceollins and Their Metabolites by Electrospray Ionization Tandem Mass Spectrometry with Precursor Ion Scanning

Phytoalexins, miRNAs and Breast Cancer: A Review of Phytochemical-mediated miRNA Regulation in Breast Cancer

Contact Info

Product

Resources

About