scholarly journals Estrogen receptor β regulates AKT activity through up-regulation of INPP4B and inhibits migration of prostate cancer cell line PC-3

2020 ◽  
Vol 117 (42) ◽  
pp. 26347-26355
Author(s):  
Surendra Chaurasiya ◽  
Wanfu Wu ◽  
Anders M. Strom ◽  
Margaret Warner ◽  
Jan-Åke Gustafsson
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Cell Line ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Akt Signaling ◽  
Inositol Polyphosphate ◽  
Androgen Independence ◽  
Beneficial Effects

Loss of the tumor suppressor, PTEN, is one of the most common findings in prostate cancer (PCa). This loss leads to overactive Akt signaling, which is correlated with increased metastasis and androgen independence. However, another tumor suppressor, inositol-polyphosphate 4-phosphatase type II (INPP4B), can partially compensate for the loss of PTEN. INPP4B is up-regulated by androgens, and this suggests that androgen-deprivation therapy (ADT) would lead to hyperactivity of AKT. However, in the present study, we found that in PCa, samples from men treated with ADT, ERβ, and INPP4B expression were maintained in some samples. To investigate the role of ERβ1 in regulation of INPPB, we engineered the highly metastatic PCa cell line, PC3, to express ERβ1. In these cells, INPP4B was induced by ERβ ligands, and this induction was accompanied by inhibition of Akt activity and reduction in cell migration. These findings reveal that, in the absence of androgens, ERβ1 induces INPP4B to dampen AKT signaling. Since the endogenous ERβ ligand, 3β-Adiol, is lost upon long-term ADT, to obtain the beneficial effects of ERβ1 on AKT signaling, an ERβ agonist should be added along with ADT.

scholarly journals Inhibition of Prostate Cancer Cell Colony Formation by the Flavonoid Quercetin Correlates with Modulation of Specific Regulatory Genes

2004 ◽  
Vol 11 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Hari Krishnan Nair ◽  
Kesava V. K. Rao ◽  
Ravikumar Aalinkeel ◽  
Supriya Mahajan ◽  
Ram Chawda ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Line ◽  
Cancer Cell ◽  
Tumor Suppressor Genes ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Suppressor Genes

ABSTRACT The natural product quercetin is a flavonoid found in many fruits and vegetables. Previous research has shown that quercetin has antitumor, anti-inflammatory, antiallergic, and antiviral activities. In the present investigation we studied the effect of quercetin on the ability of prostate cancer cell lines with various degrees of aggressive potential to form colonies in vitro. Specifically, we examined the molecular mechanisms underlying this effect, including the expression of cell cycle and tumor suppressor genes as well as oncogenes. We observed that quercetin at concentrations of 25 and 50 μM significantly inhibited the growth of the highly aggressive PC-3 prostate cancer cell line and the moderately aggressive DU-145 prostate cancer cell line, whereas it did not affect colony formation by the poorly aggressive LNCaP prostate cancer cell line or the normal fibroblast cell line BG-9. Using the gene array methodology, we found that quercetin significantly inhibited the expression of specific oncogenes and genes controlling G1, S, G2, and M phases of the cell cycle. Moreover, quercetin reciprocally up-regulated the expression of several tumor suppressor genes. In conclusion, our results demonstrate that the antitumor effects of quercetin directly correlate with the aggressive potential of prostate cancer cells and that the mechanism(s) of quercetin-mediated antitumor effects may involve up-regulation of tumor suppressor genes and reciprocal down-regulation of oncogenes and cell cycle genes. The results of these studies provide a scientific basis for the potential use of flavonoids as nutraceuticals in the chemoprevention of cancer.

scholarly journals Antiproliferative effect of rosehip tea phenolics in prostate cancer cell lines

2020 ◽  
Vol 45 (4) ◽  
pp. 423-428
Author(s):  
Ali Mert Özgönül ◽  
Aycan Aşık ◽  
Burak Durmaz ◽  
Ramin Aslaminabad ◽  
Cumhur Gündüz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Lncap Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Line ◽  
Prostate Cancer Cell Line ◽  
Antiproliferative Effect ◽  
Natural Sources

AbstractObjectivesRecently, phenolic compounds (quercetin, kaempferol, ellagic acid (EA), and myricetin) as natural sources have been suggested to be used for treatment and chemoprevention of prostate cancer. Since rosehip includes the above molecules in high concentration, we set out to investigate possible anti-proliferative effect of rosehip tea on the prostate cancer cell line.MethodsThe flavonol content of rosehip tea prepared at different temperatures and time intervals was determined first and then the antiproliferative effect of tea samples was established by adding tea samples to the prostate cancer cell line (VCaP and LNCaP).ResultsQuercetin was more effective in LNCaP cell than in VCaP cell (IC50 = 20 and 200 μM, respectively). The boiled fruit shredded at minute 7 showed the highest levels of quercetin, EA and kaempferol and the boiled fruit at minute 7 had the highest levels of kaempferol and EA. The tea samples were prepared in concentrations relevant to their IC50 values, added to the VCaP and LNCaP cell lines. The antiproliferative effect of rosehip tea on VCaP cells was slightly greater than that of LNCaP cells.ConclusionEach of the flavonols exhibits an antiproliferative effect. Our data clearly indicated that rosehip as a natural source of all flavonols had an antiproliferative effect on androgen-sensitive prostate cancer. Now that it is important to use natural sources in cancer, rosehip seems to be a promising natural product to be used to treat the prostate illness.

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