scholarly journals Abnormalities of apoptotic and cell cycle regulatory proteins in distinct histopathologic components of benign prostatic hyperplasia

2004 ◽  
Vol 7 (4) ◽  
pp. 321-326 ◽  
Author(s):  
R Gandour-Edwards ◽  
P C Mack ◽  
R W deVere-White ◽  
P H Gumerlock
Keyword(s):  
Cell Cycle ◽  
Benign Prostatic Hyperplasia ◽  
Prostatic Hyperplasia ◽  
Regulatory Proteins ◽  
Cell Cycle Regulatory Proteins

scholarly journals Cell Proliferation and Expression of Cell Cycle Regulatory Proteins that Control the G1/S Transition Are Age Dependent and Lobe Specific in the Brown Norway Rat Model of Prostatic Hyperplasia

Endocrinology ◽  
2007 ◽  
Vol 149 (1) ◽  
pp. 193-207 ◽  
Author(s):  
Jinchun Yan ◽  
Terry R. Brown
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cyclin D1 ◽  
Prostatic Hyperplasia ◽  
Regulatory Proteins ◽  
Brown Norway ◽  
Aged Rats ◽  
Young Rats ◽  
Age Dependent ◽  
Cell Cycle Regulatory Proteins

Age-dependent epithelial cell hyperplasia in the dorsal and lateral lobes of Brown Norway rats is analogous to benign prostatic hyperplasia in aging men. A major question is whether differential lobe-specific and age-dependent proliferation of cells, rather than cell survival, contributes to the hyperplasia. Although serum testosterone (T) levels decline in aged rats, active cell proliferation was detected as Ki67-positive cells in the dorsal and lateral lobes. We determined whether androgens differentially affect cell proliferation and cell-cycle regulatory proteins in the prostate lobes of young and aged rats. Castrated rats were treated with different doses of T to restore serum levels to those of intact young or aged rats. Rates of cell proliferation, measured by 5-bromodeoxyuridine labeling, peaked after 3-d T treatment in all lobes. 5-bromodeoxyuridine-labeling indices were higher in the dorsal and lateral lobes of aged than of young rats with equivalent serum T levels. No age-dependent difference was seen in the ventral lobe. Cell proliferation was marked by increased levels of cyclins D1 and E and cyclin-dependent kinases 4 and 6, decreased p27 and increased phosphorylation of Rb. Levels of cyclins D1 and E were higher in the dorsal and lateral lobes of intact and T-treated aged than young rats. Confocal immunofluorescent microscopy documented changes in cyclin-dependent kinase 4 and cyclin D1 subcellular localization. Cyclin D1 nuclear localization correlated with the time frame for cell proliferation. In conclusion, rates of cell proliferation and levels of cell-cycle regulatory proteins that control the G1/S transition exhibit lobe-specific and age-dependent differences in response to androgens.

scholarly journals Structure-Based Virtual Screening and Biological Evaluation of Peptide Inhibitors for Polo-Box Domain

Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 107 ◽  
Author(s):  
Fang Yan ◽  
Guangmei Liu ◽  
Tingting Chen ◽  
Xiaochen Fu ◽  
Miao-Miao Niu
Keyword(s):  
Cell Cycle ◽  
Virtual Screening ◽  
Fold Increase ◽  
Pharmacophore Modeling ◽  
Biological Evaluation ◽  
Peptide Inhibitors ◽  
Regulatory Proteins ◽  
Competitive Binding Assay ◽  
M Phase ◽  
Cell Cycle Regulatory Proteins

The polo-box domain of polo-like kinase 1 (PLK1-PBD) is proved to have crucial roles in cell proliferation. Designing PLK1-PBD inhibitors is challenging due to their poor cellular penetration. In this study, we applied a virtual screening workflow based on a combination of structure-based pharmacophore modeling with molecular docking screening techniques, so as to discover potent PLK1-PBD peptide inhibitors. The resulting 9 virtual screening peptides showed affinities for PLK1-PBD in a competitive binding assay. In particular, peptide 5 exhibited an approximately 100-fold increase in inhibitory activity (IC50 = 70 nM), as compared with the control poloboxtide. Moreover, cell cycle experiments indicated that peptide 5 effectively inhibited the expression of p-Cdc25C and cell cycle regulatory proteins by affecting the function of PLK1-PBD, thereby inducing mitotic arrest at the G2/M phase. Overall, peptide 5 can serve as a potent lead for further investigation as PLK1-PBD inhibitors.

scholarly journals Association of the Cell Cycle Regulatory Proteins p45SKP2and CksHs1

2001 ◽  
Vol 276 (27) ◽  
pp. 25030-25036 ◽  
Author(s):  
Lı́dia Mongay ◽  
Susana Plaza ◽  
Elena Vigorito ◽  
Carles Serra-Pagès ◽  
Jordi Vives
Keyword(s):  
Cell Cycle ◽  
Regulatory Proteins ◽  
Cell Cycle Regulatory Proteins

Apoptosis and cell-cycle regulatory proteins in colorectal carcinoma: relationship to tumour stage and patient survival

2001 ◽  
Vol 194 (4) ◽  
pp. 436-443 ◽  
Author(s):  
Mohamed A. Elkablawy ◽  
Perry Maxwell ◽  
Kate Williamson ◽  
Neil Anderson ◽  
Peter W. Hamilton
Keyword(s):  
Cell Cycle ◽  
Colorectal Carcinoma ◽  
Patient Survival ◽  
Regulatory Proteins ◽  
Tumour Stage ◽  
Cell Cycle Regulatory Proteins

scholarly journals The treatment effects of flaxseed-derived secoisolariciresinol diglycoside and its metabolite enterolactone on benign prostatic hyperplasia involve the G protein-coupled estrogen receptor 1

2016 ◽  
Vol 41 (12) ◽  
pp. 1303-1310 ◽  
Author(s):  
Guan-Yu Ren ◽  
Chun-Yang Chen ◽  
Wei-Guo Chen ◽  
Ya Huang ◽  
Li-Qiang Qin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Estrogen Receptor ◽  
Benign Prostatic Hyperplasia ◽  
G Protein ◽  
Therapeutic Potential ◽  
Prostatic Hyperplasia ◽  
Docking Simulations ◽  
G Protein Coupled

Secoisolariciresinol diglucoside (SDG), a lignan extracted from flaxseed, has been shown to suppress benign prostatic hyperplasia (BPH). However, little is known about the mechanistic basis for its anti-BPH activity. The present study showed that enterolactone (ENL), the mammalian metabolite of SDG, shared the similar binding site of G1 on a new type of membranous estrogen receptor, G-protein-coupled estrogen eceptor 1 (GPER), by docking simulations method. ENL and G1 (the specific agonist of GPER) inhibited the proliferation of human prostate stromal cell line WPMY-1 as shown by MTT assay and arrested cell cycle at the G0/G1 phase, which was displayed by propidium iodide staining following flow cytometer examination. Silencing GPER by short interfering RNA attenuated the inhibitory effect of ENL on WPMY-1 cells. The therapeutic potential of SDG in the treatment of BPH was confirmed in a testosterone propionate-induced BPH rat model. SDG significantly reduced the enlargement of the rat prostate and the number of papillary projections of prostatic alveolus and thickness of the pseudostratified epithelial and stromal cells when comparing with the model group. Mechanistic studies showed that SDG and ENL increased the expression of GPER both in vitro and in vivo. Furthermore, ENL-induced cell cycle arrest may be mediated by the activation of GPER/ERK pathway and subsequent upregulation of p53 and p21 and downregulation of cyclin D1. This work, in tandem with previous studies, will enhance our knowledge regarding the mechanism(s) of dietary phytochemicals on BPH prevention and ultimately expand the scope of adopting alternative approaches in BPH treatment.

Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis

2000 ◽  
Vol 278 (4) ◽  
pp. F515-F529 ◽  
Author(s):  
Stuart J. Shankland ◽  
Gunter Wolf
Keyword(s):  
Cell Cycle ◽  
Renal Function ◽  
Renal Disease ◽  
Cell Injury ◽  
Critical Role ◽  
Regulatory Proteins ◽  
Specific Cell ◽  
Cell Cycle Proteins ◽  
Proliferation And Apoptosis ◽  
Cell Cycle Regulatory Proteins

The response to glomerular and tubulointerstitial cell injury in most forms of renal disease includes changes in cell number (proliferation and apoptosis) and cell size (hyerptrophy). These events typically precede and may be reponsible for the accumulation of extracellular matrix proteins that leads to a decrease in renal function. There is increasing evidence showing that positive (cyclins and cyclin-dependent kinases) and negative (cyclin-dependent kinase inhibitors) cell cycle regulatory proteins have a critical role in regulating these fundamental cellular responses to immune and nonimmune forms of injury. Data now show that altering specific cell cycle proteins affects renal cell proliferation and improves renal function. Equally exciting is the expanding body of literature showing novel biological roles for cell cycle proteins in the regulation of cell hypertrophy and apoptosis. With increasing understanding of the role for cell cyle regulatory proteins in renal disease comes the hope for potential therapeutic inverventions.

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