scholarly journals Molecular and Cellular Reports A Pharmacological Study of the Action of Esculetin on Human Prostate Cancer Cells

2021 ◽  
Author(s):  
Chung-Ren Jan ◽  
Jue-Long Wang ◽  
Wei-Chuan Liao ◽  
Rong-An Lin ◽  
Shu-Han Chang ◽  
...  
Keyword(s):  
Cell Death ◽  
Pharmacological Study ◽  
Cell Types ◽  
Cellular Responses ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Acetoxymethyl Ester ◽  
Prostate Cells ◽  
Kinase C

Abstract Esculetin is a derivative of coumarin, and is the dominant, vigorous component of the conventional Chinese medicine Cortex Fraxini. Recently, the molecular pathway study and clinical use of Cortex Fraxini and esculetin are becoming intensive. In vitro, esculetin has been shown to provoke apoptotic responses via mitochondrial routes and other cellular responses in diverse cell types. The action of esculetin on cytosolic Ca2+ concentration ([Ca2+]i) in prostate cells is unknown. [Ca2+]i were assayed by applying fura-2, a fluorescent Ca2+-sensitive probe. WST-1 was used to measure cell death. Esculetin at doses of 25–100 µM provoked [Ca2+]i raises. Removing external Ca2+ decreased the response by 15%. Esculetin (100 µM) provoked Mn2+ entry implying Ca2+ influx. Esculetin-provoked Ca2+ influx was suppressed by half by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA) and inhibitor (GF109203X); and by three inhibitors of store-operated Ca2+ channels: nifedipine, econazole and SKF96365. In the absence of Ca2+, pretreatment with the endoplasmic reticulum (ER) Ca2+ pump suppressor thapsigargin completely suppressed esculetin-provoked [Ca2+]i raises. Suppression of phospholipase C (PLC) with U73122 eliminated esculetin-provoked [Ca2+]i raises. Esculetin at 20–70 µM caused death of cells, which was not prevented by incubation with the Ca2+ binder 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). In sum, in PC3 prostate cells, esculetin provoked [Ca2+]i raises by provoking PLC-associated Ca2+ discharge from ER and Ca2+ influx via PKC-sensitive store-operated Ca2+ influx. Additionally, esculetin provoked Ca2+-dissociated cell death.

scholarly journals Distinct roles for the RNA-binding protein Staufen1 in prostate cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kristen A. Marcellus ◽  
Tara E. Crawford Parks ◽  
Shekoufeh Almasi ◽  
Bernard J. Jasmin
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Rna Binding ◽  
Prostate Cancer Cell ◽  
Rna Binding Protein ◽  
Migration And Invasion ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Prostate Cells

Abstract Background Prostate cancer is one of the most common malignant cancers with the second highest global rate of mortality in men. During the early stages of disease progression, tumour growth is local and androgen-dependent. Despite treatment, a large percentage of patients develop androgen-independent prostate cancer, which often results in metastases, a leading cause of mortality in these patients. Our previous work on the RNA-binding protein Staufen1 demonstrated its novel role in cancer biology, and in particular rhabdomyosarcoma tumorigenesis. To build upon this work, we have focused on the role of Staufen1 in other forms of cancer and describe here the novel and differential roles of Staufen1 in prostate cancer. Methods Using a cell-based approach, three independent prostate cancer cell lines with different characteristics were used to evaluate the expression of Staufen1 in human prostate cancer relative to control prostate cells. The functional impact of Staufen1 on several key oncogenic features of prostate cancer cells including proliferation, apoptosis, migration and invasion were systematically investigated. Results We show that Staufen1 levels are increased in all human prostate cancer cells examined in comparison to normal prostate epithelial cells. Furthermore, Staufen1 differentially regulates growth, migration, and invasion in the various prostate cancer cells assessed. In LNCaP prostate cancer cells, Staufen1 regulates cell proliferation through mTOR activation. Conversely, Staufen1 regulates migration and invasion of the highly invasive, bone metastatic-derived, PC3 prostate cells via the activation of focal adhesion kinase. Conclusions Collectively, these results show that Staufen1 has a direct impact in prostate cancer development and further demonstrate that its functions vary amongst the prostate cancer cell types. Accordingly, Staufen1 represents a novel target for the development of much-needed therapeutic strategies for prostate cancer.

Differential effects of transforming growth factor β on human prostate cancer cells in vitro

1989 ◽  
Vol 62 (1) ◽  
pp. 79-87 ◽  
Author(s):  
George Wilding ◽  
Gerhard Zugmeier ◽  
Cornelius Knabbe ◽  
Katherine Flanders ◽  
Edward Gelmann
Keyword(s):  
Prostate Cancer ◽  
Growth Factor ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Differential Effects

scholarly journals Regulation of Fertility, Survival, and Cuticle Collagen Function by the Caenorhabditis elegans eaf-1 and ell-1 Genes

2011 ◽  
Vol 286 (41) ◽  
pp. 35915-35921 ◽  
Author(s):  
Liquan Cai ◽  
Binh L. Phong ◽  
Alfred L. Fisher ◽  
Zhou Wang
Keyword(s):  
Caenorhabditis Elegans ◽  
Cell Types ◽  
Transcriptional Elongation ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Transcription Factor Family ◽  
Collagen Expression ◽  
Extracellular Matrix Components ◽  
Multiple Cell

EAF2, an androgen-regulated protein, interacts with members of the ELL (eleven-nineteen lysine-rich leukemia) transcription factor family and also acts as a tumor suppressor. Although these proteins control transcriptional elongation and perhaps modulate the effects of other transcription factors, the mechanisms of their actions remain largely unknown. To gain new insights into the biology of the EAF2 and ELL family proteins, we used Caenorhabditis elegans as a model to explore the in vivo roles of their worm orthologs. Through the use of transgenic worms, RNAi, and an eaf-1 mutant, we found that both genes are expressed in multiple cell types throughout the worm life cycle and that they play important roles in fertility, survival, and body size regulation. ELL-1 and EAF-1 likely contribute to these activities in part through modulating cuticle synthesis, given that we observed a disrupted cuticle structure in ell-1 RNAi-treated or eaf-1 mutant worms. Consistent with disruption of cuticle structure, loss of either ELL-1 or EAF-1 suppressed the rol phenotype of specific collagen mutants, possibly through the control of dpy-3, dpy-13, and sqt-3 collagen gene expression. Furthermore, we also noted the regulation of collagen expression by ELL overexpression in PC3 human prostate cancer cells. Together, these results reveal important roles for the eaf-1 and ell-1 genes in the regulation of extracellular matrix components.

scholarly journals NF-κB activation enhances cell death by antimitotic drugs in human prostate cancer cells

2010 ◽  
Vol 9 (1) ◽  
pp. 182 ◽  
Author(s):  
Ricardo Parrondo ◽  
Alicia Pozas ◽  
Teresita Reiner ◽  
Priyamvada Rai ◽  
Carlos Perez-Stable
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Antimitotic Drugs

Mitogen stimulation of Na+-H+ exchange: differential involvement of protein kinase C

1987 ◽  
Vol 253 (2) ◽  
pp. C219-C229 ◽  
Author(s):  
L. L. Muldoon ◽  
G. A. Jamieson ◽  
A. C. Kao ◽  
H. C. Palfrey ◽  
M. L. Villereal
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cell Types ◽  
Intact Cells ◽  
Kinase C ◽  
Protein Kinase C Activity ◽  
Human Fibroblast Strains ◽  
Stimulation Of

The mitogen-induced activation of Na+-H+ exchange was investigated in two cultured human fibroblast strains (HSWP and WI-38 cells) that, based on previous studies, differed in their response to the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) (L. M. Vincentini and M. L. Villereal, Proc. Natl. Acad. Sci. USA 82: 8053-8056, 1985). The role of protein kinase C in the activation of Na+-H+ exchange was investigated by comparing the effects of TPA on Na+ influx, in vitro phosphorylation, and in vivo phosphorylation in both cell types. Although both cell types have significant quantities of protein kinase C activity that can be activated by TPA in intact cells, the addition of TPA to intact cells stimulates Na+ influx in WI-38 cells but not in HSWP cells, indicating that in HSWP cells the stimulation of protein kinase C is not sufficient to activate the Na+-H+ exchanger. Cells were then depleted of protein kinase C activity by chronic treatment with high doses of TPA. Both HSWP and WI-38 cells were rendered protein kinase C deficient by this treatment as determined by in vitro and in vivo phosphorylation studies. Protein kinase C-deficient HSWP cells lose the ability for TPA to inhibit the serum-induced activation of Na+-H+ exchange, but there is no reduction in the stimulation of Na+ influx by serum, bradykinin, vasopressin, melittin, or vanadate, indicating that protein kinase C activity is not necessary for the mitogen-induced activation of Na+-H+ exchange in HSWP cells by agents known to stimulate phosphatidylinositol turnover (G. A. Jamieson and M. Villereal. Arch. Biochem. Biophys. 252: 478-486, 1987). In contrast, depletion of protein kinase C activity in WI-38 cells significantly reduces both the TPA- and the serum-induced activation of the Na+-H+ exchange system, suggesting that protein kinase C activity is necessary for at least a portion of the mitogen-induced activation of the Na+-H+ exchanger in WI-38 cells. These results indicate that the mechanisms for regulating Na+-H+ exchange can differ dramatically between different types of fibroblasts.

Blueberry flavonoids inhibit matrix metalloproteinase activity in DU145 human prostate cancer cells

2005 ◽  
Vol 83 (5) ◽  
pp. 637-643 ◽  
Author(s):  
Michael D Matchett ◽  
Shawna L MacKinnon ◽  
Marva I Sweeney ◽  
Katherine T Gottschall-Pass ◽  
Robert A.R Hurta
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Prostate ◽  
Response To Treatment ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
The Matrix ◽  
Ecm Degradation

Regulation of the matrix metalloproteinases (MMPs), the major mediators of extracellular matrix (ECM) degradation, is crucial to regulate ECM proteolysis, which is important in metastasis. This study examined the effects of 3 flavonoid-enriched fractions (a crude fraction, an anthocyanin-enriched fraction, and a proanthocyanidin-enriched fraction), which were prepared from lowbush blueberries (Vaccinium angustifolium), on MMP activity in DU145 human prostate cancer cells in vitro. Using gelatin gel electrophoresis, MMP activity was evaluated from cells after 24-hr exposure to blueberry fractions. All fractions elicited an ability to decrease the activity of MMP-2 and MMP-9. Of the fractions tested, the proanthocyanidin-enriched fraction was found to be the most effective at inhibiting MMP activity in these cells. No induction of either necrotic or apoptotic cell death was noted in these cells in response to treatment with the blueberry fractions. These findings indicate that flavonoids from blueberry possess the ability to effectively decrease MMP activity, which may decrease overall ECM degradation. This ability may be important in controlling tumor metastasis formation.Key words: blueberry flavonoids, MMP activity, prostate cancer cells.

Sign in / Sign up

Export Citation Format

Share Document