Interactions of methoxyacetic acid with androgen receptor

Bagchi, Gargi; Hurst, Christopher H.; Waxman, David J.

doi:10.1016/j.taap.2008.03.015

Cited by 22 publications

(23 citation statements)

References 61 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MAA exposure is associated with various developmental and reproductive toxicities in both rodents and humans, including neural toxicity, blood and immune disorders, limb degeneration and testicular toxicity [8,9,10]. The mechanisms of MAA-induced toxicities are multiple.…”

Section: Introductionmentioning

confidence: 99%

Aminomethylphosphonic Acid and Methoxyacetic Acid Induce Apoptosis in Prostate Cancer Cells

Parajuli¹,

Zhang²,

Liu³

et al. 2015

IJMS

View full text Add to dashboard Cite

Aminomethylphosphonic acid (AMPA) and its parent compound herbicide glyphosate are analogs to glycine, which have been reported to inhibit proliferation and promote apoptosis of cancer cells, but not normal cells. Methoxyacetic acid (MAA) is the active metabolite of ester phthalates widely used in industry as gelling, viscosity and stabilizer; its exposure is associated with developmental and reproductive toxicities in both rodents and humans. MAA has been reported to suppress prostate cancer cell growth by inducing growth arrest and apoptosis. However, it is unknown whether AMPA and MAA can inhibit cancer cell growth. In this study, we found that AMPA and MAA inhibited cell growth in prostate cancer cell lines (LNCaP, C4-2B, PC-3 and DU-145) through induction of apoptosis and cell cycle arrest at the G1 phase. Importantly, the AMPA-induced apoptosis was potentiated with the addition of MAA, which was due to downregulation of the anti-apoptotic gene baculoviral inhibitor of apoptosis protein repeat containing 2 (BIRC2), leading to activation of caspases 7 and 3. These results demonstrate that the combination of AMPA and MAA can promote the apoptosis of prostate cancer cells, suggesting that they can be used as potential therapeutic drugs in the treatment of prostate cancer.

show abstract

Section: Introductionmentioning

confidence: 99%

Aminomethylphosphonic Acid and Methoxyacetic Acid Induce Apoptosis in Prostate Cancer Cells

Parajuli¹,

Zhang²,

Liu³

et al. 2015

IJMS

View full text Add to dashboard Cite

show abstract

“…Ha et al found that AR levels are regulated by the AKT [ 14 ]. Activation of AKT causes downstream effects such as increases in co-activator binding and chromatin modifications associated with an increase in AR transcriptional output [ 15 ]. AKT, also known as protein kinase B, is crucial for regulation of cell proliferation, differentiation, apoptosis, and migration [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Androgen receptor promotes gastric cancer cell migration and invasion via AKT-phosphorylation dependent upregulation of matrix metalloproteinase 9

Zhang

Zang

et al. 2014

Oncotarget

View full text Add to dashboard Cite

Androgen receptor (AR) plays an important role in many kinds of cancers. However, the molecular mechanisms of AR in gastric cancer (GC) are poorly characterized. Here, we investigated the role of AR in GC cell migration, invasion and metastatic potential. Our data showed that AR expression was positively correlated with lymph node metastasis and late TNM stages. These findings were accompanied by activation of AKT and upregulation of matrix metalloproteinase 9 (MMP9). AR overexpression induced increases in GC cell migration, invasion and proliferation in vitro and in vivo. These effects were attenuated by inhibition of AKT, AR and MMP9. AR overexpression upregulated MMP9 protein levels, whereas this effect was counteracted by AR siRNA. Inhibition of AKT by siRNA or an inhibitor (MK-2206 2HC) decreased AR protein expression in both stably transfected and parental SGC-7901 cells. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that AR bound to the AR-binding sites of the MMP9 promoter. In summary, AR overexpression induced by AKT phosphorylation upregulated MMP9 by binding to its promoter region to promote gastric carcinogenesis. The AKT/AR/MMP9 pathway plays an important role in GC metastasis and may be a novel therapeutic target for GC treatment.

show abstract

“…In addition, MAA treatment markedly increased the expression of cyp17a1 (steroid 17α-hydroxylase/17,20-lyase) and ABP/Shbg in a mouse testicular Leydig cell line TM3 while suppressing Igfbp3 (insulin-like growth factor binding protein-3) expression by ~90%. Deregulation of these genes may alter the synthesis and action of androgen in a manner that contributes to MAA-induced testicular toxicity 37) .…”

Section: Androgen Receptor-associated Effects Of Maamentioning

confidence: 99%

Embryo- and Testicular-toxicities of Methoxyacetate and the Related: a Review on Possible Roles of One-carbon Transfer and Histone Modification

Yamazoe¹,

Yamada

Mitsumori³

2015

Food Safety

View full text Add to dashboard Cite

Methoxyacetate (MAA), formed by the metabolisms of ethylene glycol monomethyl ether (2-methoxyethanol), di-(2methoxyethyl) phthalate and 1,6-dimethoxyhexane, is known to be a teratogenic and testicular toxicant in experimental animals. MAA is known to inhibit histone deacetylase and is associated with lactate-carrying monocarboxylate transporter expressed in Sertoli and fetal cells. In cells of rapid division, nucleosomal histone exchanges occur through the methyl and acetyl modifications and rates of nucleic acid syntheses are elevated with consumption of cellular energy. These phenomena are considered to associate with MAA-mediated teratogenicity and phase-selective spermatocyte disorders, and also suggest a mutual adverse-outcome pathway in which MAA-mediated histone deacetylase inhibition is involved through p21 activation as the early events. In addition, a possible functional relationship of one-carbon transferring folate/S-adenosyl methionine cycle with testicular metabolisms of sarcosine and creatine is envisioned. Thus, the mechanisms underlying the MAA toxicities will be discussed in relation to the current understanding of the involvement of the epigenetic phenomena and cell-specific metabolisms.

show abstract

Interactions of methoxyacetic acid with androgen receptor

Cited by 22 publications

References 61 publications

Aminomethylphosphonic Acid and Methoxyacetic Acid Induce Apoptosis in Prostate Cancer Cells

Aminomethylphosphonic Acid and Methoxyacetic Acid Induce Apoptosis in Prostate Cancer Cells

Androgen receptor promotes gastric cancer cell migration and invasion via AKT-phosphorylation dependent upregulation of matrix metalloproteinase 9

Embryo- and Testicular-toxicities of Methoxyacetate and the Related: a Review on Possible Roles of One-carbon Transfer and Histone Modification

Contact Info

Product

Resources

About