1α,25-Dihydroxyvitamin D3 Actions in LNCaP Human Prostate Cancer Cells Are Androgen-Dependent*

Abstract We and others have recently shown that 1α,25-dihydroxyvitamin D3 [1,25-(OH)2D3] significantly inhibits cell proliferation and increases secretion of prostate-specific antigen (PSA) in LNCaP cells, an androgen-responsive human prostate cancer cell line. The present study was designed to investigate the possible interactions between 1,25-(OH)2D3 and androgens in the regulation of LNCaP cellular function. LNCaP cell growth was dose-dependently inhibited by 1,25-(OH)2D3 (60% inhibition at 10 nm) when cells were cultured in medium supplemented with FBS (FBS medium). 1,25-(OH)2D3-treated cells showed a 5-fold increase in PSA secretion, similar to the increase seen in dihydrotestosterone (DHT)-treated cells. In combination, 1,25-(OH)2D3 and DHT synergistically enhanced PSA secretion 22-fold. This synergistic effect was even greater when cells were cultured in medium supplemented with charcoal-stripped serum (CSS medium), where endogenous steroids are substantially depleted. Under these conditions, 1,25-(OH)2D3 and DHT together stimulated PSA secretion up to 50-fold over the untreated control. Radioligand binding assays and Western blot analyses showed that the androgen receptor (AR) content was increased significantly by 1,25-(OH)2D3 at 48 h. Furthermore, the steady-state mRNA level of AR was up-regulated approximately 2-fold by 1,25-(OH)2D3 at 24 h. When cells were grown in CSS medium, 1,25-(OH)2D3 alone no longer inhibited cell growth or induced PSA secretion. Titration experiments revealed that the addition of DHT at 1 nm to the medium restored the antiproliferative activity of 1,25-(OH)2D3. Conversely, an antiandrogen, Casodex, completely blocked 1,25-(OH)2D3 antiproliferative and PSA stimulation activities when cells were cultured in FBS medium. In conclusion, these results demonstrate that the antiproliferative and PSA induction activities of 1,25-(OH)2D3 in LNCaP cells are dependent upon androgen action and that AR up-regulation by 1,25-(OH)2D3 likely contributes to the synergistic actions of 1,25-(OH)2D3 and DHT in these cells.

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Proteasome inhibitor PS-341 down-regulates prostate-specific antigen (PSA) and induces growth arrest and apoptosis of androgen-dependent human prostate cancer LNCaP cells

Cancer Science ◽

10.1111/j.1349-7006.2004.tb02215.x ◽

2004 ◽

Vol 95 (3) ◽

pp. 271-275 ◽

Cited By ~ 36

Author(s):

Takayuki Ikezoe ◽

Yang Yang ◽

Tsuyako Saito ◽

H. Phillip Koeffler ◽

Hirokuni Taguchi

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Proteasome Inhibitor ◽

Specific Antigen ◽

Growth Arrest ◽

Human Prostate ◽

Human Prostate Cancer ◽

Lncap Cells

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Knocking down claudin receptors leads to a decrease in prostate cancer cell migration, cell growth, cell viability and clonogenic cell survival

Molecular Biomedicine ◽

10.1186/s43556-021-00053-0 ◽

2021 ◽

Vol 2 (1) ◽

Author(s):

Qiang Liu ◽

Hongliang Shen ◽

Andrew Naguib ◽

Robert M. Weiss ◽

Darryl T. Martin

Keyword(s):

Prostate Cancer ◽

Cell Migration ◽

Cell Growth ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Human Prostate ◽

Human Prostate Cancer ◽

Lncap Cells ◽

Prostate Cancer Cells ◽

Cancer Cell Growth

AbstractProstate cancer is the most common solid organ malignancy in the United States, and has the highest probability of all cancers in becoming invasive. New molecular targets are needed to define and impede the growth and progression of advanced prostate cancers. Claudins (Cldns) are transmembrane proteins that regulate paracellular permeability and cell polarity, and their levels are elevated in many human cancers such as breast, ovarian, pancreatic, and prostatic cancers. Previously, we found that Cldn3 and Cldn4 are expressed in aggressive high-grade human prostate cancer specimens. We and others have shown that there are higher levels of Cldn3 and Cldn4 in metastatic human prostate cancer cells than in normal human prostate cells. The result of targeting Cldn3 and Cldn4 expression on the growth and viability of prostate cancer cells has not been elucidated. Human prostate cancer PC3 and LNCaP cells were transfected with Cldn3 or -4 small interfering RNAs (siRNAs). Cldn3/Cldn4 siRNA treatment resulted in a greater than 85% decrease in the protein levels of Cldn3 and Cldn4, which was accompanied by a 30–40% decrease in prostate cancer cell growth and a 60–65% reduction in cell viability. There was decreased cell migration with Cldn3 and Cldn4 siRNA in both PC3 and LNCaP cells and a 60–75% decrease in the number of clones when treated with siCldn3 or siCldn4 compared to control. Knocking down Cldn3/Cldn4 affects prostate cancer cell growth and survival and may have therapeutic implications.

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[6]-Gingerol Decreases Clonogenicity And Radioresistance of Human Prostate Cancer Cells

Clinical Oncology and Research ◽

10.31487/j.cor.2019.05.07 ◽

2019 ◽

pp. 1-3

Author(s):

Maria Helena Bellini ◽

Silva JPL ◽

Teixeira LF

Keyword(s):

Prostate Cancer ◽

Cancer Cell Line ◽

Zingiber Officinale ◽

Prostate Cancer Cell Line ◽

Clonogenic Survival ◽

Human Prostate ◽

Antitumor Action ◽

Human Prostate Cancer ◽

Lncap Cells ◽

Malignant Tumours

The phenolic compound [6]-Gingerol, isolated from Zingiber officinale, has been demonstrated to have antitumor activity for different types of malignant tumours. Prostate cancer is the most common malignancy among males worldwide, being the second leading cause of cancer death in men. In the present study, we investigated the antitumor action of [6]-Gingerol on a human prostate cancer cell line (LNCaP). Our data shows that [6]-Gingerol treatment induced a dose-dependent decrease in the cell viability. Compared with the vehicle control, the cell viabilities were 79.90 ± 3.56% and 53.06 ± 7.82% when the LNCaP cells were exposed to 150 μg/mL and 300 μg/mL of [6]-Gingerol, respectively. The treatment of LNCaP with 300 µM of [6]-Gingerol led to a significant reduction (~25%) on the clonogenic survival of these cells. Furthermore, [6]-gingerol acted as a radiosensitizer for LNCaP cells. The pretreatment of these cells with [6]-Gingerol significantly enhanced the killing effects of ionizing radiation with a dose enhancement ratio of 1.25. Our results demonstrate the anti-tumour activities of [6]-Gingerol. Further studies are needed to elucidate the mechanisms involved.

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Anti-androgen receptor activity of apoptotic CK2 inhibitor CX4945 in human prostate cancer LNCap cells

Bioorganic & Medicinal Chemistry Letters ◽

10.1016/j.bmcl.2012.07.031 ◽

2012 ◽

Vol 22 (17) ◽

pp. 5470-5474 ◽

Cited By ~ 10

Author(s):

Byung Jun Ryu ◽

Seung-hwa Baek ◽

Jiyeon Kim ◽

Su Jung Bae ◽

Sung-Youn Chang ◽

...

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

Receptor Activity ◽

Human Prostate ◽

Human Prostate Cancer ◽

Lncap Cells ◽

Androgen Receptor Activity ◽

Ck2 Inhibitor

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1α,25-Dihydroxyvitamin D3 (calcitriol) and its analogue, 19-nor-1α,25(OH)2D2, potentiate the effects of ionising radiation on human prostate cancer cells

British Journal of Cancer ◽

10.1038/sj.bjc.6601161 ◽

2003 ◽

Vol 89 (4) ◽

pp. 746-753 ◽

Cited By ~ 42

Author(s):

N Dunlap ◽

G G Schwartz ◽

D Eads ◽

S D Cramer ◽

A B Sherk ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Ionising Radiation ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Dihydroxyvitamin D3

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Selenite Treatment Inhibits LAPC-4 Tumor Growth and Prostate-Specific Antigen Secretion in a Xenograft Model of Human Prostate Cancer

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2008.07.005 ◽

2008 ◽

Vol 72 (3) ◽

pp. 935-940 ◽

Cited By ~ 15

Author(s):

Rumi S. Bhattacharyya ◽

Bryan Husbeck ◽

David Feldman ◽

Susan J. Knox

Keyword(s):

Prostate Cancer ◽

Tumor Growth ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Xenograft Model ◽

Human Prostate ◽

Human Prostate Cancer

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Anticancer activity of midostaurin in hormone refractory human prostate cancer DU145 cells

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v11i2.24954 ◽

2016 ◽

Vol 11 (2) ◽

pp. 378

Author(s):

Jin-Jun Sun ◽

Shi-Feng Kan ◽

Guan-Xing Sun

Keyword(s):

Prostate Cancer ◽

Kinase Inhibitor ◽

Cancer Cell Line ◽

Prostate Cancer Cell Line ◽

Nerve Cells ◽

Human Prostate ◽

Human Prostate Cancer ◽

Du145 Cells ◽

Hormone Refractory

We tried a new method of prostate cancer treatment by inducing in vitro differentiation which resulted in reduction of cancer cells growth. A protein kinase inhibitor, midostaurin's ability to trigger the human prostate cancer cell line, DU145 to segregate into nerve cells was studied. Midostaurin (100 nM) suppressed the growth of DU145 cells but without change in the number of dead cells. Midostaurin started to extend neurites on DU145 cells after 24 hours and differentiated into nerve cells by 72 hours. The microtubule was stabilized by tau protein and its mRNA expression showed time-dependent increase in midostaurin-treated DU145 cells. At the same time, the amount of acetylcholinesterase was also increased. The midostaurin-treated DU145 cells showed 40% less activity than control in the colony forming assay. The results suggests that midostaurin can induce differentiation of DU145 cells into nerve cells.

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