scholarly journals Bisphenol A and its analogues disrupt centrosome cycle and microtubule dynamics in prostate cancer

2017 ◽  
Vol 24 (2) ◽  
pp. 83-96 ◽  
Author(s):  
Shuk-Mei Ho ◽  
Rahul Rao ◽  
Sarah To ◽  
Emma Schoch ◽  
Pheruza Tarapore
Keyword(s):  
Prostate Cancer ◽  
Bisphenol A ◽  
Consumer Products ◽  
Microtubule Dynamics ◽  
Serum Starvation ◽  
Cyclin Dependent Kinase ◽  
Microtubule Organization ◽  
Developmental Exposure ◽  
Cancer Initiation ◽  
Structural Analogues

Humans are increasingly exposed to structural analogues of bisphenol A (BPA), as BPA is being replaced by these compounds in BPA-free consumer products. We have previously shown that chronic and developmental exposure to BPA is associated with increased prostate cancer (PCa) risk in human and animal models. Here, we examine whether exposure of PCa cells (LNCaP, C4-2) to low-dose BPA and its structural analogues (BPS, BPF, BPAF, TBBPA, DMBPA and TMBPA) affects centrosome amplification (CA), a hallmark of cancer initiation and progression. We found that exposure to BPA, BPS, DMBPA and TBBPA, in descending order, increased the number of cells with CA, in a non-monotonic dose–response manner. Furthermore, cells treated with BPA and their analogues initiated centrosome duplication at 8 h after release from serum starvation, significantly earlier in G-1 phase than control cells. This response was attended by earlier release of nucleophosmin from unduplicated centrosomes. BPA-exposed cells exhibited increased expression of cyclin-dependent kinaseCDK6and decreased expression of CDK inhibitors (p21Waf1/CIP1andp27KIP1). Using specific antagonists for estrogen/androgen receptors, CA in the presence of BPA or its analogues was likely to be mediated via ESR1 signaling. Change in microtubule dynamics was observed on exposure to these analogues, which, for BPA, was accompanied by increased expression of centrosome-associated proteinCEP350. Similar to BPA, chronic treatment of cells with DMBPA, but not other analogues, resulted in the enhancement of anchorage-independent growth. We thus conclude that selected BPA analogues, similar to BPA, disrupt centrosome function and microtubule organization, with DMBPA displaying the broadest spectrum of cancer-promoting effects.

scholarly journals Quo Vadis Advanced Prostate Cancer Therapy? Novel Treatment Perspectives and Possible Future Directions

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2228
Author(s):  
Jana Kvízová ◽  
Vladimíra Pavlíčková ◽  
Eva Kmoníčková ◽  
Tomáš Ruml ◽  
Silvie Rimpelová
Keyword(s):  
Prostate Cancer ◽  
Advanced Prostate Cancer ◽  
Kinase Inhibitors ◽  
Diagnostic Methods ◽  
Common Disease ◽  
Cyclin Dependent Kinase ◽  
Future Directions ◽  
Prostate Cancer Therapy ◽  
Quo Vadis ◽  
Antiandrogen Therapy

Prostate cancer is a very common disease, which is, unfortunately, often the cause of many male deaths. This is underlined by the fact that the early stages of prostate cancer are often asymptomatic. Therefore, the disease is usually detected and diagnosed at late advanced or even metastasized stages, which are already difficult to treat. Hence, it is important to pursue research and development not only in terms of novel diagnostic methods but also of therapeutic ones, as well as to increase the effectiveness of the treatment by combinational medicinal approach. Therefore, in this review article, we focus on recent approaches and novel potential tools for the treatment of advanced prostate cancer; these include not only androgen deprivation therapy, antiandrogen therapy, photodynamic therapy, photothermal therapy, immunotherapy, multimodal therapy, but also poly(ADP-ribose) polymerase, Akt and cyclin-dependent kinase inhibitors.

scholarly journals Developmental Programming: Prenatal Bisphenol A Induces Non-Monotonic Changes in Epigenetic Modulators in Metabolic Tissues of Female Sheep

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A485-A485
Author(s):  
Muraly Puttabyatappa ◽  
Joseph Norman Ciarelli ◽  
Vasantha Padmanabhan
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Bisphenol A ◽  
Dna Methyltransferases ◽  
Size Analysis ◽  
Developmental Exposure ◽  
Epigenetic Machinery ◽  
The Impact ◽  
Higher Doses ◽  
Female Sheep

Abstract Developmental exposure to endocrine disruptor bisphenol A (BPA) is associated \with metabolic defects during adulthood in the female sheep. These are characterized by peripheral insulin resistance and increase in negative mediators of insulin sensitivity such as oxidative stress in metabolic tissues, lipotoxicity in liver and muscle and adipocyte hypertrophy in visceral (VAT) and subcutaneous (SAT) adipose tissue. Conceivably, developmental impact of BPA on regulators of insulin sensitivity involves changes in epigenetic machinery and mediated via changes in expression of enzymes that induce covalent modifications of DNA and histone. To determine the impact of prenatal BPA exposure on epigenetic enzymes [DNA methyltransferases (DNMT), histone deacetylases (HDAC), histone acetyl transferase EP300, histone methylases (SUV39H1, SMYD3 and EZH2) and histone demethylase KDM1A], metabolic tissues (liver, muscle, VAT and SAT) were collected from 21-month-old female offspring born to mothers treated with 0, 0.05, 0.5, or 5 mg/kg/day of BPA from days 30-90 of gestation. Data were analyzed by Cohen’s effect size analysis and large magnitude differences (Cohens d>0.8) discussed. In liver, prenatal BPA induced: 1) a decrease in DNMT1 and 3B at all doses and DNMT3A at the highest dose, 2) a decrease in histone deacetylase HDAC3 as opposed to increase in acetylase EP300 at the highest dose, 3) a decrease in SUV39H1 at the two higher doses, and 4) an increase in EZH2 only with 0.5 mg dose. The prenatal BPA-induced changes in muscle include: 1) increases in expression of DNMTs and EP300 at all doses, 2) an increase in SUV39H1 at 0.5 mg dose and EZH2 at 0.05 and 0.5 mg doses, and 3) decreases in SMYD3 at the lowest dose and KDM1A with 0.05 and 5 mg doses. Prenatal BPA treatment also induced depot-specific changes at the adipose tissue level. In the VAT prenatal BPA induced: 1) increases in expression of all DNMTs examined 2) increases in HDAC2 at all doses except HDAC3 only at 0.05 and 0.5mg dose and 3) increases in histone acetylase EP300 at all doses. In SAT BPA induced: 1) decrease in DNMT3A at 0.5mg and increase at 5 mg, 2) decreases in HDAC1 and HDAC2 at the lowest dose, 3) an increase in HDAC3 at the medium dose, and 4) a decrease in EP300 at the lowest dose. Contrasting changes in histone methylation modifying enzymes were also evident between VAT and SAT manifested as increases in SUV39H1 at the two higher doses and SMYD3 at all three doses in the VAT as opposed to decrease in SUV39H1 and SMYD3 at 0.05 and 0.5 mg doses and EZH2 and KDM1A at the lowest dose in the SAT. These findings indicating developmental exposure to BPA induces non-monotonic dose responses in epigenetic modifying enzymes are consistent with the premise that changes in epigenetic machinery underlie the metabolic disruptions induced by prenatal BPA treatment likely accounting for the tissue specific changes in insulin sensitivity. (support by R01-ES-016541)

Developmental exposure to low-dose of bisphenol A alters maternal behaviour in rats

2011 ◽  
Vol 205 ◽  
pp. S294
Author(s):  
S. Boudalia ◽  
L. Decocq ◽  
R. Berges ◽  
M. Canivenclavier
Keyword(s):  
Bisphenol A ◽  
Low Dose ◽  
Maternal Behaviour ◽  
Developmental Exposure

scholarly journals The many ways to make a luminal cell and a prostate cancer cell

2015 ◽  
Vol 22 (6) ◽  
pp. T187-T197 ◽  
Author(s):  
Douglas W Strand ◽  
Andrew S Goldstein
Keyword(s):  
Prostate Cancer ◽  
Stem Cell ◽  
Prostate Cancer Cell ◽  
Stem Cell Differentiation ◽  
Cell Populations ◽  
Self Renewal ◽  
Signaling Mechanisms ◽  
Cancer Initiation ◽  
The Many ◽  
Multiple Cells

Research in the area of stem/progenitor cells has led to the identification of multiple stem-like cell populations implicated in prostate homeostasis and cancer initiation. Given that there are multiple cells that can regenerate prostatic tissue and give rise to prostate cancer, our focus should shift to defining the signaling mechanisms that drive differentiation and progenitor self-renewal. In this article, we will review the literature, present the evidence and raise important unanswered questions that will help guide the field forward in dissecting critical mechanisms regulating stem-cell differentiation and tumor initiation.

scholarly journals 2185 The effects of autoimmune inflammation on proliferation, differentiation, and androgen receptor signaling in adult prostate stem cells

2018 ◽  
Vol 2 (S1) ◽  
pp. 31-31
Author(s):  
Paula Cooper ◽  
Hsing-Hui Wang ◽  
Meaghan Broman ◽  
Emery Goossens ◽  
Hristos Kaimakliotis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Androgen Receptor ◽  
3D Cell Culture ◽  
Androgen Receptor Signaling ◽  
Autoimmune Inflammation ◽  
Cancer Initiation ◽  
Study Population ◽  
Tissue Recombination ◽  
Survival Mechanisms

OBJECTIVES/SPECIFIC AIMS: The primary goal of this project is to verify findings from a murine prostatitis model in the human setting. METHODS/STUDY POPULATION: Methods include primary cell isolation and culture, FACS, adoptive transfer, 3D cell culture, histology, immunofluorescence, xenograft, and tissue recombination. The study population includes patients undergoing HoLEP or radical prostatectomy due to hyperplasia or adjacent bladder or prostate cancer. RESULTS/ANTICIPATED RESULTS: Having verified similar sensitivities to androgen receptor (AR) inhibitors between naive murine and human basal prostate stem cells, we anticipate that autoimmune inflammation in humans affects the response of basal prostate stem cells in a manner similar to the murine setting as well. This includes increased proliferation, increased differentiation, and decreased response to AR inhibitors. DISCUSSION/SIGNIFICANCE OF IMPACT: The identification of survival mechanisms used by basal prostate stem cells in an androgen deprived environment may give insight to the process by which prostate cancer becomes androgen independent. The effect of inflammation on proliferation, survival, and AR signaling in these cells may also provide information relevant to cancer initiation and progression.

NF-κB signaling promotes castration-resistant prostate cancer initiation and progression

2020 ◽  
Vol 211 ◽  
pp. 107538
Author(s):  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Afshan F. Nawas ◽  
Monica Bautista ◽  
Nikki A. Delk
Keyword(s):  
Prostate Cancer ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Cancer Initiation
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