scholarly journals Calcitriol-Induced Apoptosis in LNCaP Cells Is Blocked By Overexpression of Bcl-21

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 10-17 ◽  
Author(s):  
Sarah E. Blutt ◽  
Timothy J. McDonnell ◽  
Tara C. Polek ◽  
Nancy L. Weigel
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Vitamin D ◽  
Cancer Cells ◽  
Mineral Metabolism ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Apoptotic Pathway ◽  
Induced Apoptosis

Abstract While the role of vitamin D in bone and mineral metabolism has been investigated extensively, the role of the vitamin D receptor in other tissues is less well understood. 1,25-dihydroxyvitamin D3 (calcitriol) can act as a differentiating agent in normal tissues and can inhibit the growth of many cancer cell lines including LNCaP prostate cancer cells. We have shown previously that calcitriol causes LNCaP cell accumulation in the G0/G1 phase of the cell cycle. In this study, we demonstrate that calcitriol also induces apoptosis of LNCaP cells. The calcitriol-induced apoptosis is accompanied by a down-regulation of Bcl-2 and Bcl-XL proteins, both of which protect cells from undergoing apoptosis. Other proteins important in apoptotic control, Bax, Mcl-1, and Bcl-Xs, are unaffected by calcitriol treatment. We find that overexpression of Bcl-2 blocks calcitriol-induced apoptosis and reduces, but does not eliminate, calcitriol-induced growth inhibition. We conclude that both regulation of cell cycle and the apoptotic pathway are involved in calcitriol action in prostate cancer cells.

Role of Vitamin D as an Anti-Proliferative Compound on Prostate Cancer

2013 ◽  
Vol 30 (3) ◽  
pp. 123-128
Author(s):  
Ahmad Humayan Kabir ◽  
Ferdhos Khan ◽  
Mamunur Rashid Sarkar
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Cancer Cells ◽  
Human Prostate Cancer ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Prostate Cell ◽  
Clear Band ◽  
Potential Use

Summary The reason of prostate cancer is the mutation in the prostate cell. The present study was aimed at determining the effects of different concentrations of vitamin D on the anti-proliferative action of 24,25(OH)2D3 applied on LNCaP (cell line of human prostate cancer) cells. It was evident from the results that vitamin D having concentrations of 10-9nM showed the best anti-proliferative action on prostate cancer cells (LNCaP cells) compared to other concentrations used. Most of the receptors were expressed at 10-9nM resulting clear band in agarose gel image. Results also revealed that both nVDR and AR receptors (androgen receptors) were expressed well when treated with 10-9nM and 10-10nM concentrations of 24,25(OH)2D3. These findings confirm the potential use of vitamin D as an anti-proliferative compound against prostate cancer cells.

scholarly journals p53 Is Required for 1,25-Dihydroxyvitamin D3-Induced G0 Arrest But Is Not Required for G1 Accumulation or Apoptosis of LNCaP Prostate Cancer Cells

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 50-60 ◽  
Author(s):  
Tara C. Polek ◽  
LaMonica V. Stewart ◽  
Elizabeth J. Ryu ◽  
Michael B. Cohen ◽  
Elizabeth A. Allegretto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Lines ◽  
Dominant Negative ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Induction Of Apoptosis

Abstract 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] is an effective agent for inhibiting the growth of prostate cancer cells including LNCaP and PC-3 cell lines. However, the extent of growth inhibition in these cell lines differs because LNCaP cells are much more responsive than PC-3 cells. Previous studies in LNCaP cells have shown that 1,25-(OH)2D3 treatment results in G0/G1 cell cycle accumulation, loss of Ki67 expression, and induction of apoptosis. One difference between the two cell lines is that PC-3 cells lack functional p53, a protein that plays roles both in cell cycle regulation and induction of apoptosis. In this study, the role of p53 in 1,25-(OH)2D3 action was examined using the p53-negative PC-3 cells and a line of LNCaP cells, called LN-56, in which p53 function was shut off using a dominant negative p53 fragment. We found that treatment with 1,25-(OH)2D3 extensively inhibits growth of LN-56 prostate cancer cells lacking p53, but in contrast to the parental LNCaP cells, the LN-56 cells recover rapidly. Moreover, in prostate cancer cells, the synergism between 1,25-(OH)2D3 and 9-cis retinoic acid appears to be dependent on the presence of functional p53; however, 1,25-(OH)2D3-mediated induction of G1 cell cycle accumulation and induction of apoptosis is not.

scholarly journals Role of Bax in quercetin-induced apoptosis in human prostate cancer cells

2008 ◽  
Vol 75 (12) ◽  
pp. 2345-2355 ◽  
Author(s):  
Dae-Hee Lee ◽  
Miroslaw Szczepanski ◽  
Yong J. Lee
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Induced Apoptosis

scholarly journals GADD45γ: a New Vitamin D-Regulated Gene that Is Antiproliferative in Prostate Cancer Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (10) ◽  
pp. 4654-4664 ◽  
Author(s):  
Omar Flores ◽  
Kerry L. Burnstein
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cell Cycle ◽  
Vitamin D ◽  
Androgen Receptor ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibits proliferation of normal and malignant prostate epithelial cells at least in part through inhibition of G1 to S phase cell cycle progression. The mechanisms of the antiproliferative effects of 1,25-(OH)2D3 have yet to be fully elucidated but are known to require the vitamin D receptor. We previously developed a 1,25-(OH)2D3-resistant derivative of the human prostate cancer cell line, LNCaP, which retains active vitamin D receptors but is not growth inhibited by 1,25-(OH)2D3. Gene expression profiling revealed two novel 1,25-(OH)2D3-inducible genes, growth arrest and DNA damage-inducible gene gamma (GADD45γ) and mitogen induced gene 6 (MIG6), in LNCaP but not in 1,25-(OH)2D3-resistant cells. GADD45γ up-regulation was associated with growth inhibition by 1,25-(OH)2D3 in human prostate cancer cells. Ectopic expression of GADD45γ in either LNCaP or ALVA31 cells resulted in G1 accumulation and inhibition of proliferation equal to or greater than that caused by 1,25-(OH)2D3 treatment. In contrast, ectopic expression of MIG6 had only minimal effects on cell cycle distribution and proliferation. Whereas GADD45γ has been shown to be induced by androgens in prostate cancer cells, up-regulation of GADD45γ by 1,25-(OH)2D3 was not dependent on androgen receptor signaling, further refuting a requirement for androgens/androgen receptor in vitamin D-mediated growth inhibition. These data introduce two novel 1,25-(OH)2D3-regulated genes and establish GADD45γ as a growth-inhibitory protein in prostate cancer. Furthermore, the induction of GADD45γ gene expression by 1,25-(OH)2D3 may mark therapeutic response in prostate cancer.

scholarly journals hPEBP4 Resists TRAIL-induced Apoptosis of Human Prostate Cancer Cells by Activating Akt and Deactivating ERK1/2 Pathways

2006 ◽  
Vol 282 (7) ◽  
pp. 4943-4950 ◽  
Author(s):  
Hongzhe Li ◽  
Xiaojian Wang ◽  
Nan Li ◽  
Jianming Qiu ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Potential Candidate ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Efficient Treatment ◽  
Akt Activation ◽  
Du145 Cells ◽  
Induced Apoptosis

The treatment options available for prostate cancer are limited because of its resistance to therapeutic agents. Thus, a better understanding of the underlying mechanisms of the resistance of prostate cancer will facilitate the discovery of more efficient treatment protocols. Human phosphatidylethanolamine-binding protein 4 (hPEBP4) is recently identified by us as an anti-apoptotic molecule and a potential candidate target for breast cancer treatment. Here we found the expression levels of hPEBP4 were positively correlated with the severity of clinical prostate cancer. Furthermore, hPEBP4 was not expressed in TRAIL-sensitive DU145 prostate cancer cells, but was highly expressed in TRAIL-resistant LNCaP cells, which show highly activated Akt. Interestingly, hPEBP4 overexpression in TRAIL-sensitive DU145 cells promoted Akt activation but inhibited ERK1/2 activation. The hPEBP4-overexpressing DU145 cells became resistant to TRAIL-induced apoptosis consequently, which could be reversed by PI3K inhibitors. In contrast, silencing of hPEBP4 in TRAIL-resistant LNCaP cells inhibited Akt activation but increased ERK1/2 activation, resulting in their sensitivity to TRAIL-induced apoptosis that was restored by the MEK1 inhibitor. Therefore, hPEBP4 expression in prostate cancer can activate Akt and deactivate ERK1/2 signaling, leading to TRAIL resistance. We also demonstrated that hPEBP4-mediated resistance to TRAIL-induced apoptosis occurred downstream of caspase-8 and at the level of BID cleavage via the regulation of Akt and ERK pathways, and that hPEBP4-regulated ERK deactivation was upstream of Akt activation in prostate cancer cells. Considering that hPEBP4 confers cellular resistance to TRAIL-induced apoptosis and is abundantly expressed in poorly differentiated prostate cancer, silencing of hPEBP4 suggests a promising approach for prostate cancer treatment.

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