scholarly journals Resveratrol Attenuates the Proliferation of Prostatic Stromal Cells in Benign Prostatic Hyperplasia by Regulating Cell Cycle Progression, Apoptosis, Signaling Pathways, BPH Markers, and NF- κB Activity

2021 ◽  
Vol 22 (11) ◽  
pp. 5969
Author(s):  
Jowon Jang ◽  
Junhui Song ◽  
Jiyun Lee ◽  
Sung-Kwon Moon ◽  
Bokyung Moon
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Stromal Cells ◽  
Cell Cycle Progression ◽  
Apoptotic Cell ◽  
Nuclear Factor Κb ◽  
Binding Activity ◽  
Prostatic Hyperplasia ◽  
Phase Cell ◽  
Extracellular Signal

Resveratrol can inhibit cell proliferation and metastasis and induce apoptosis. However, the mechanisms of action through which resveratrol inhibits the abnormal proliferation of prostate stromal cells, causing prostatic hyperplasia, have not been fully elucidated. Here, we evaluated the inhibitory effects of resveratrol on cell° proliferation associated with prostatic hyperplasia using WPMY-1 cells. Our results showed that resveratrol inhibited the proliferation of WPMY-1 cells via the induction of G0/G1-phase cell cycle arrest, which was caused by downregulated expression of cyclins and cyclin-dependent kinases regulated by increased p21WAF1 and p27KIP1 expression level. In addition, resveratrol treatment suppressed the phosphorylation of phosphatidylinositol 3-kinase/AKT and extracellular signal-regulated kinase 1/2. The expression levels of molecular markers affecting prostate development were also reduced by treatment with resveratrol. Finally, resveratrol attenuated the binding activity of the transcription factor nuclear factor-κB in WPMY-1 cells, and accelerated apoptotic cell death via intrinsic cascade pathway. These results indicate that resveratrol may be useful for the prevention or treatment of prostatic hyperplasia.

scholarly journals Umbelliferone Ameliorates Benign Prostatic Hyperplasia by Inhibiting Cell Proliferation and G1/S Phase Cell Cycle Progression through Regulation of STAT3/E2F1 Axis

2021 ◽  
Vol 22 (16) ◽  
pp. 9019
Author(s):  
Hyo-Jung Kim ◽  
Bo-Ram Jin ◽  
Hyo-Jin An
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Benign Prostatic Hyperplasia ◽  
Cell Cycle Progression ◽  
Underlying Mechanism ◽  
Prostatic Hyperplasia ◽  
S Phase ◽  
Nuclear Antigen ◽  
Phase Cell ◽  
Proliferative Effect

Umbelliferone (UMB), also known as 7-hydroxycoumarin, is a derivative of coumarin, which is widely found in many plants such as carrots, coriander, and garden angelica. Although many studies have already revealed the various pharmacological properties of UMB, its effect on benign prostatic hyperplasia (BPH) remains unclear. Therefore, the present study aimed to elucidate the underlying mechanism of the anti-proliferative effect of UMB in a human benign prostatic hyperplasia cell line (BPH-1), as well as its ameliorative effect on BPH in testosterone propionate (TP)-induced rats. The results showed that UMB exerts an anti-proliferative effect in BPH-1 cells by modulating the signal transducer and activator of transcription 3 (STAT3)/E2F transcription factor 1 (E2F1) axis. UMB treatment not only inhibited androgen/androgen receptor (AR) signaling-related markers, but also downregulated the overexpression of G1/S phase cell cycle-related markers. In TP-induced rats, UMB administration demonstrated an anti-BPH effect by significantly reducing prostate size, weight, and epithelial thickness. In addition, UMB suppressed cell proliferation by reducing the expression of proliferating cell nuclear antigen (PCNA) and p-STAT3 (Tyr 705) in prostate tissue following TP injection. These findings suggest that UMB has pharmacological effects against BPH.

scholarly journals E2F1 Induces KIF26A Transcription and Promotes Cell Cycle Progression via CDK–RB–E2Fs Feedback Loop in Breast Cancer

2021 ◽  
Vol 10 ◽  
Author(s):  
Jing Xu ◽  
Lei Liu ◽  
Ranran Ma ◽  
Yawen Wang ◽  
Xu Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Feedback Loop ◽  
Cell Cycle Progression ◽  
Transcriptional Factor ◽  
Phase Cell ◽  
Luciferase Reporter ◽  
Cycle Progression ◽  
The Core

ObjectiveThe aim of this study was to investigate the role of KIF26A in breast cancer.MethodqRT-PCR and immunohistochemistry were conducted to explore KIF26A expression and functional contribution to breast cancer development. MTS, EDU, colony formation assays, and flow cytometry analysis were conducted to assess cell proliferation characteristics and cell cycle progression. A series of 5′-flanking region deletion plasmids and mutating the binding site, with the luciferase reporter assay, were used to identify the core promotor region of KIF26A. The prediction by software and construction of the transcriptional factor plasmids were used to identify the transcriptional factor. Chromatin immunoprecipitation assay could demonstrate transcriptional factor directly binding to the KIF26A promoter. Human Genome Oligo Microarray Assay and gene ontology (GO) and pathway analyses were used to predict the downstream pathway.ResultsOur results showed that in breast cancer tissues, elevated KIF26A expression was significantly correlated with lymph node metastasis. KIF26A could promote proliferation and G0/G1 phase cell cycle progression in breast cancer cells. The core promoter region of the human KIF26A gene was located upstream of the transcription start site at position −395 to −385. The transcriptional factor E2F1 was shown to activate KIF26A expression. Furthermore, KIF26A was shown to inhibit the expression of p21, then activate CDK–RB–E2Fs pathway. The elevated E2F1 can activate the cell cycle progression and the KIF26A expression, forming feedback loop.ConclusionsThe present study demonstrated that KIF26A, directly upregulated by E2F1, promoted cell proliferation and cell cycle progression via CDK–RB–E2Fs feedback loop in breast cancer.

Application of the nuclear factor-κB inhibitor BAY 11-7085 for the treatment of endometriosis: an in vitro study

2007 ◽  
Vol 293 (1) ◽  
pp. E16-E23 ◽  
Author(s):  
Kaei Nasu ◽  
Masakazu Nishida ◽  
Tami Ueda ◽  
Akitoshi Yuge ◽  
Noriyuki Takai ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Caspase 3 ◽  
In Vitro Study ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Phase Cell ◽  
High Recurrence Rate ◽  
Induced Apoptosis

Most of the current medical treatments for endometriosis aim to downregulate estrogen activity. However, a high recurrence rate after medical treatment has been the most significant problem. BAY 11-7085, a soluble inhibitor of NK-κB activation, has been shown to inhibit cell proliferation and induce apoptosis of a variety of cells. To examine the potential application of BAY 11-7085 in the treatment of endometriosis, we investigated the effects of this agent on the cell proliferation and apoptosis of cultured ovarian endometriotic cyst stromal cells (ECSCs) by a modified methylthiazole tetrazolium assay, a 5-bromo-2′-deoxyuridine incorporation assay, and internucleosomal DNA fragmentation assays. The effect of BAY 11-7085 on the cell cycle of ECSCs was also determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSCs with Western blot analysis. BAY 11-7085 significantly inhibited the cell proliferation and DNA synthesis of ECSCs and induced apoptosis and the G0/G1 phase cell cycle arrest of these cells. Additionally, downregulation of the B-cell lymphoma/leukemia-2 (Bcl-2) and Bcl-XLexpression with simultaneous activation of caspase-3, -8, and -9 was observed in ECSCs after treatment with BAY 11-7085. These results suggest that BAY 11-7085 induces apoptosis of ECSCs by suppressing antiapoptotic proteins, and that caspase-3-, -8-, and -9-mediated cascades are involved in this mechanism. Therefore, BAY 11-7085 could be used as a therapeutic agent for the treatment of endometriosis.

scholarly journals Role of Interleukin-18 in Modulation of Oral Carcinoma Cell Proliferation

2006 ◽  
Vol 2006 ◽  
pp. 1-6 ◽  
Author(s):  
Athip Nilkaeo ◽  
Suthinee Bhuvanath
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Tumor Regression ◽  
Apoptotic Cell ◽  
Interleukin 18 ◽  
Cycle Arrest ◽  
Dose Dependent Fashion ◽  
Oral Cancer Cells

Interleukin-18 (IL-18), a proinflammatory cytokine, is produced by oral epithelia and carcinoma cells and implicated in tumor regression. Since its direct biological effect on oral cancer cells is not well defined, in this study, we employed a KB cell line to test IL-18 activity. Recombinant human IL-18 significantly inhibited KB cell proliferation in a dose-dependent fashion (P<.05) without increasing cytotoxicity. Analysis of its mode of action showed that IL-18 induced cell cycle arrest in the S phase; however, it did not trigger apoptotic cell death. Findings in this study indicate that the suppression of KB cell proliferation was attributed to the modulation of cell cycle progression, providing a new role of this cytokine in antitumor mechanisms.

scholarly journals Incaspitolide A extracted from Carpesium cernuum induces apoptosis in vitro via the PI3K/AKT pathway in benign prostatic hyperplasia

2021 ◽  
Author(s):  
Xiaoyue Chen ◽  
Jingrui Song ◽  
Dongbo Yuan ◽  
Qing Rao ◽  
Kehua Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Benign Prostatic Hyperplasia ◽  
Cell Cycle Arrest ◽  
Cyclin B1 ◽  
Prostatic Hyperplasia ◽  
Phase Cell ◽  
Prolonged Treatment ◽  
Akt Pathway ◽  
Cycle Arrest

Benign prostatic hyperplasia (BPH) is a common disease that occurs mainly in older men. The pathogenesis of BPH is complex and patients face a prolonged treatment course, and novel drugs with better selectivity and lower toxicity are required. incaspitolide A (compound TMJ-12) is a germacrane-type sesquiterpenoid compound extracted from the plant Carpesium carnuum. Extracts of C. carnuum are known to exert suppressive effects on BPH-1 cells. In this study, we investigated the molecular mechanisms underlying the suppressive effect of TMJ-12 specifically on BPH-1 cells. A cytotoxicity assay indicated that TMJ-12 inhibited BPH-1 cell proliferation, while flow cytometry assays showed that TMJ-12 induced G2/M phase cell cycle arrest and the apoptosis of BPH-1 cells. TMJ-12 was also shown to regulate the expression of several apoptosis- and cell cycle-related proteins, namely Bcl-2, Bax, Bad, Caspase-9, Caspase-3, CDK1, Cyclin B1, CDC25C, and c-Myc, among others. Collapse of the mitochondrial membrane potential (ΔΨm) following exposure to TMJ-12 was detected with the JC-1 staining assay. Further investigation revealed that treatment with TMJ-12 inhibited the PI3K/AKT pathway by increasing the expression of PTEN. Taken together, the results suggest that TMJ-12 prevents BPH-1 cell proliferation via the PI3K/AKT pathway by inducing apoptosis and cell cycle arrest.

Ribociclib Cytotoxicity Alone Or Combined With Progesterone And/Or Mitotane In In Vitro Adrenocortical Carcinoma Cells

Endocrinology ◽  
2021 ◽  
Author(s):  
Andrea Abate ◽  
Elisa Rossini ◽  
Mariangela Tamburello ◽  
Marta Laganà ◽  
Deborah Cosentini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Viability ◽  
Adrenocortical Carcinoma ◽  
Cell Cycle Progression ◽  
Apoptotic Cell ◽  
Target Therapy ◽  
Drug Induced ◽  
Cycle Progression

Abstract Mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC). The regimen to be added to mitotane is a chemotherapy with etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Target-therapy agents represent a new promising approach to cancer therapy. Among these, a preeminent role is played by agents that interfere with cell cycle progression, such as CDK4/6-inhibitors. Here, we investigated whether ribociclib could induce a cytotoxic effect both in ACC cell line and patient-derived primary cell cultures, alone or in combined settings. Cell viability was determined by MTT assay while cell proliferation was evaluated by direct count. Binary combination experiments were performed using Chou and Talalay method. Gene expression was analyzed by qRT-PCR while protein expression was evaluated by immunofluorescence. A double staining assay revealed that ribociclib induced a prevalent apoptotic cell death. Cell cycle analysis was performed to evaluate the effect of ribociclib treatment on cell cycle progression in ACC cell models. Our results indicated that ribociclib was cytotoxic and reduced the cell proliferation rate. The effect on cell viability was enhanced when ribociclib was combined with progesterone and/or mitotane. The effect of ribociclib on cell cycle progression revealed a drug-induced cell accumulation in G2 phase. The positive relationship underlined by our results between ribociclib, progesterone and mitotane strengthen the clinical potential of this combination.

scholarly journals SIPA1 boosts migration and proliferation, and blocks apoptosis of glioma by activating the phosphorylation of the FAK signaling pathway

2021 ◽  
Author(s):  
Yuan Du ◽  
Shenglan Li ◽  
Tong Zhou ◽  
Jing Zhao ◽  
Jiguang Liu
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Apoptotic Cell ◽  
Glioma Cells ◽  
Phase Cell ◽  
Cycle Progression ◽  
Protein Levels ◽  
Normal Tissues ◽  
Regulatory Effects

Background: We aimed to analyze the regulatory effects of SIPA1 (signal-induced proliferation-associated protein 1) on glioma progression and the dominant signaling pathway. Methods: Differential level of SIPA1 in glioma and normal tissues and cells was determined. Migratory, proliferative, apoptotic and cell cycle progression changes in A172 cells with overexpression or knockdown of SIPA1 were examined. Finally, protein levels of phosphorylated FAKs in A172 cells intervened by SIPA1 and the FAK inhibitor PF-562271 were detected. Results: SIPA1 was upregulated in glioma cases. Knockdown of SIPA1 reduced migratory and proliferative rates of glioma cells, increased apoptotic cell rate, and declined cell ratio in S phase. Cell cycle proteins were also downregulated by knockdown of SIPA1. SIPA1 upregulated phosphorylated FAKs in A172 cells and thus boosted malignant phenotypes of glioma. Conclusions: SIPA1 is upregulated in glioma that boosts migratory and proliferative potentials of glioma cells by activating the phosphorylation of the FAK signaling pathway.

scholarly journals p63 regulates cell proliferation and cell cycle progression-associated genes in stromal cells of giant cell tumor of the bone

2012 ◽  
Vol 42 (2) ◽  
pp. 437-443 ◽  
Author(s):  
CAROL PO YING LAU ◽  
PATRICK KWOK SHING NG ◽  
MAN SHAN LI ◽  
STEPHEN KWOK WING TSUI ◽  
LIN HUANG ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Cell Cycle Progression ◽  
Cell Tumor ◽  
Cycle Progression
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