Effect of dimethoxycurcumin beyond degradation of androgen receptor

Wang, Weiming; Cheng, Hsiao-Chun; Liu, Yingchun; Chang, Yung‐Lung; Liu, Shuting

doi:10.1016/j.dsi.2011.09.001

Cited by 8 publications

(18 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been proposed that the AR and its downstream pathways, but not androgen, may be alternative targets in androgen-AR pathway-dominant diseases. Specifically, ASC-J9, a curcumin derivative that is in clinical trial for acne treatment, has been reported to possess AR-degradation–enhancing activity [33, 42]. …”

Section: Discussionmentioning

confidence: 99%

Minoxidil may suppress androgen receptor-related functions

et al. 2014

View full text Add to dashboard Cite

Although minoxidil has been used for more than two decades to treat androgenetic alopecia (AGA), an androgen-androgen receptor (AR) pathway-dominant disease, its precise mechanism of action remains elusive. We hypothesized that minoxidil may influence the AR or its downstream signaling. These tests revealed that minoxidil suppressed AR-related functions, decreasing AR transcriptional activity in reporter assays, reducing expression of AR targets at the protein level, and suppressing AR-positive LNCaP cell growth. Dissecting the underlying mechanisms, we found that minoxidil interfered with AR-peptide, AR-coregulator, and AR N/C-terminal interactions, as well as AR protein stability. Furthermore, a crystallographic analysis using the AR ligand-binding domain (LBD) revealed direct binding of minoxidil to the AR in a minoxidil-AR-LBD co-crystal model, and surface plasmon resonance assays demonstrated that minoxidil directly bound the AR with a Kd value of 2.6 μM. Minoxidil also suppressed AR-responsive reporter activity and decreased AR protein stability in human hair dermal papilla cells. The current findings provide evidence that minoxidil could be used to treat both cancer and age-related disease, and open a new avenue for applications of minoxidil in treating androgen-AR pathway-related diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Minoxidil may suppress androgen receptor-related functions

et al. 2014

View full text Add to dashboard Cite

show abstract

“…27 Subsequently, dimethoxycurcumin has been used to treat prostate cancer because this curcumin derivative is able to induce the degradation of an overexpressed androgen receptor. 29 This finding is reflected in our family with NPS carrying the LMX1b-R198X mutant, the unwanted stability and mislocalization of which might cause the haploinsufficiency of the wild-type LMX1b transcription factor. 29 This finding is reflected in our family with NPS carrying the LMX1b-R198X mutant, the unwanted stability and mislocalization of which might cause the haploinsufficiency of the wild-type LMX1b transcription factor.…”

Section: Discussionmentioning

confidence: 79%

“…28 Recently, more transcription factors have been found as targets for dimethoxycurcumin, which potentially allows this agent to be used in other diseases. 29 This finding is reflected in our family with NPS carrying the LMX1b-R198X mutant, the unwanted stability and mislocalization of which might cause the haploinsufficiency of the wild-type LMX1b transcription factor. Considering the developmental processes in which LMX1b is likely to exert a fundamental role in different organs and tissues, using the downstream responsive IL-6 gene as a model might not be helpful in deciphering the complicated relationship between the genotypic and phenotypic manifestations of NPS.…”

Section: Discussionmentioning

confidence: 79%

Biochemical properties of the recurrent LMX1b truncated mutant carried in a Taiwanese family with nail-patella syndrome

et al. 2014

View full text Add to dashboard Cite

We demonstrated that loss of function might not be the only way for mutated LMX1b to cause haploinsufficiency as the main pathogenic mechanism for NPS. LMX1b-R198X has less nuclear localization and higher stability than the wild-type protein; consequently, it might function as a competitor to sequester other effectors by protein-protein interaction to interfere with downstream transcriptional events.

show abstract

“…Plenty of studies have shown that DMC possesses many pharmacological activities, even more effective in fighting numerous cancer cells, and the antitumor mechanism is similar to its parent compound curcumin [2]. Even at a very low concentration, DMC could induce epigenetic changes in leukemia cells, and the effect was ten-fold higher than curcumin [3].…”

Section: Introductionmentioning

confidence: 99%

Absorption and Elimination of Dimethoxycurcumin, An Active Analogue of Curcumin

Zhang¹,

Yang²,

Wang³

et al. 2017

dtbh

View full text Add to dashboard Cite

Abstract. Dimethoxycurcumin (DMC) is an active analogue of curcumin with superior efficacy in various disease models. However, pharmacokinetic research on DMC is limited.The present study was designed to investigate oral absorption and excretion of DMC, as well as making a thorough examination on in vivo metabolism. DMC in rat plasma, bile, urine and feces was quantitated by High performance liquid chromatography(HPLC), and liquid chromatography-mass spectra(LC-MS) detection was performed for metabolites identification. The results showed that the oral bioavailability of DMC was 15 times higher than curcumin. DMC was metabolized in vivo via a similar pathway to curcumin. However, accumulated excretion of DMC was 13.21%±1.83%in bile, and the metabolic degree was less extensive than curcumin. Excretion of DMC was less than 1% in urine, and about 65% in feces. All the findings indicated similar in vivo disposition characteristics of curcuminoid.

show abstract

Effect of dimethoxycurcumin beyond degradation of androgen receptor

Cited by 8 publications

References 46 publications

Minoxidil may suppress androgen receptor-related functions

Minoxidil may suppress androgen receptor-related functions

Biochemical properties of the recurrent LMX1b truncated mutant carried in a Taiwanese family with nail-patella syndrome

Absorption and Elimination of Dimethoxycurcumin, An Active Analogue of Curcumin

Contact Info

Product

Resources

About