Lignans Isolated fromCampylotropis hirtella(Franch.) Schindl. Decreased Prostate Specific Antigen and Androgen Receptor Expression in LNCaP Cells

2008 ◽  
Vol 56 (16) ◽  
pp. 6928-6935 ◽  
Author(s):  
Hui-Ying Han ◽  
Xiang-Hong Wang ◽  
Nai-Li Wang ◽  
Ming-Tat Ling ◽  
Yong-Chuan Wong ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Lncap Cells

scholarly journals Role of Testosterone Levels on the Combinatorial Effect of Boswellia serrata Extract and Enzalutamide on Androgen Dependent LNCaP Cells and in Patient Derived Cells

2021 ◽  
Vol 20 ◽  
pp. 153473542199682
Author(s):  
Prathesha Pillai ◽  
Ginil Kumar Pooleri ◽  
Shantikumar V. Nair
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Early Stage ◽  
Therapeutic Option ◽  
Specific Antigen ◽  
Cell Killing ◽  
Receptor Expression ◽  
Lncap Cells ◽  
Boswellia Serrata ◽  
Physiological Serum

Co-therapy with herbal extracts along with current clinical drugs is being increasingly recognized as a useful complementary treatment for cancer. The anti-cancer property of the phyto-derivative acetyl-11 keto β boswellic acid (AKBA) has been studied in many cancers, including prostate cancer. However, the whole extract of the gum resin Boswellia serrata (BS) and anti-androgen enzalutamide has not been explored in prostate cancer to date. We hypothesized that the BS extract containing 30% (AKBA) with enzalutamide acted synergistically in the early phase of cancer, especially in LNCaP cells, by inhibiting androgen receptor (AR) and by reducing cell proliferation, and further, that the extract would be superior to the action of the active ingredient AKBA when used alone or in combination with enzalutamide. To test our hypothesis, we treated LNCaP cells with BS extract or AKBA and enzalutamide both individually and in combination to analyze cell viability under different levels of dihydrotestosterone (DHT). The inhibition of androgen receptor (AR) followed by the expression of prostate-specific antigen (PSA) and the efflux mechanism of the cells were analyzed to determine the effect of the combination on the cellular mechanism. Cells derived from prostate cancer patients were also tested with the combination. Only 6 µM enzalutamide along with BS in the range of 4.1 µg/ml to 16.4 µg/ml gave the best synergistic results with nearly 50% cell killing even though standard enzalutamide doses were as high as 48 µM. Cell killing was most effective at intermediate DHT concentrations of approximately 1 nM, which corresponds to normal physiological serum levels of DHT. The Pgp expression level and the androgen receptor expression levels were reduced under the combination treatment; the former helping to minimize drug efflux and the latter by reducing the sensitivity to hormonal changes. Furthermore, the combination reduced the PSA level secreted by the cells. In contrast, AKBA could not achieve the needed synergism for adequate cell killing at equivalent concentrations. The combination of enzalutamide and BS extract containing 30% AKBA because of their synergistic interaction is an attractive therapeutic option for treating early stage (hormone-dependent) prostate cancer and is superior to the use of AKBA alone.

Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells

2004 ◽  
Vol 286 (6) ◽  
pp. E927-E931 ◽  
Author(s):  
Yasuhisa Fujii ◽  
Satoru Kawakami ◽  
Yohei Okada ◽  
Yukio Kageyama ◽  
Kazunori Kihara
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Prostate Specific Antigen ◽  
Specific Antigen ◽  
Activin A ◽  
Prostate Tissue ◽  
Dependent Manner ◽  
Lncap Cells

Activins are multifunctional growth and differentiation factors and stimulate FSH-β gene expression and FSH secretion by the pituitary gonadotropes. Follistatins bind activin, resulting in the neutralization of activin bioactivity. The activin/follistatin system is present in the prostate tissue. Prostate-specific antigen (PSA) plays an important role in male reproductive physiology as well as being very important as a tumor marker for prostate cancer. Thus the regulation of PSA has important clinical implications. Previous studies showed that PSA is primarily regulated by androgens. In the present study, we evaluated the direct effects of activin A on the proliferation and PSA production of prostate cancer LNCaP cells, which express functional activin receptors and androgen receptor and PSA. LNCaP cells were treated with activin A and 5α-dihydrotestosterone (DHT) with or without their antagonists (follistatin or the nonsteroidal anti-androgen bicalutamide). Activin A decreased cell growth of LNCaP cells in a dose-dependent manner, whereas DHT increased it in a biphasic manner. In contrast to their opposing actions on cell growth, both activin A and DHT upregulated PSA gene expression and increased PSA secretion by LNCaP cells. The effects of activin A and DHT to increase PSA production were synergistic or additive. Follistatin or bicalutamide was without effect on cell growth or PSA production. The effects of activin A on LNCaP cells were blocked by follistatin, not by bicalutamide, whereas effects of DHT were prevented by bicalutamide, not by follistatin. Activin A upregulates PSA production, and the effect is through an androgen receptor-independent pathway. The activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to upregulate PSA in vivo.

MODIFICATION OF PROLIFERATION, APOPTOSIS AND ANDROGEN RECEPTOR EXPRESSION OF LNCAP CELLS BY DIET POLYPHENOLS

2006 ◽  
Vol 5 (2) ◽  
pp. 168
Author(s):  
A. Ferruelo ◽  
J. Angulo ◽  
C. Pascual-mateo ◽  
I. Romero ◽  
M. Lujan ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Receptor Expression ◽  
Androgen Receptor Expression ◽  
Lncap Cells

scholarly journals Negative Modulation of Androgen Receptor Transcriptional Activity by Daxx

2004 ◽  
Vol 24 (24) ◽  
pp. 10529-10541 ◽  
Author(s):  
Ding-Yen Lin ◽  
Hsin-I Fang ◽  
Ai-Hong Ma ◽  
Yen-Sung Huang ◽  
Yeong-Shiau Pu ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Prostate Specific Antigen ◽  
Transcriptional Activity ◽  
Specific Antigen ◽  
Antigen Expression ◽  
Lncap Cells ◽  
Negative Regulators ◽  
Amino Terminal

ABSTRACT The transcriptional activity of the androgen receptor (AR) modulated by positive or negative regulators plays a critical role in controlling the growth and survival of prostate cancer cells. Although numerous positive regulators have been identified, negative regulators of AR are less well understood. We report here that Daxx functions as a negative AR coregulator through direct protein-protein interactions. Overexpression of Daxx suppressed AR-mediated promoter activity in COS-1 and LNCaP cells and AR-mediated prostate-specific antigen expression in LNCaP cells. Conversely, downregulation of endogenous Daxx expression by RNA interference enhances androgen-induced prostate-specific antigen expression in LNCaP cells. In vitro and in vivo interaction studies revealed that Daxx binds to both the amino-terminal and the DNA-binding domain of the AR. Daxx proteins interfere with the AR DNA-binding activity both in vitro and in vivo. Moreover, sumoylation of AR at its amino-terminal domain is involved in Daxx interaction and trans-repression. Together, these findings not only provide a novel role of Daxx in controlling AR transactivation activity but also uncover the mechanism underlying sumoylation-dependent transcriptional repression of the AR.

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