scholarly journals Effect of Celastrol on Growth Inhibition of Prostate Cancer Cells through the Regulation of hERG ChannelIn Vitro

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Nan Ji ◽  
Jinjun Li ◽  
Zexiong Wei ◽  
Fanhu Kong ◽  
Hongyan Jin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Apoptosis ◽  
Herg Channel ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Du145 Cells ◽  
Dose Dependent

Objective.To explore the antiprostate cancer effects of Celastrol on prostate cancer cells’ proliferation, apoptosis, and cell cycle distribution, as well as the correlation to the regulation of hERG.Methods.DU145 cells were treated with various concentrations of Celastrol (0.25–16.0 μmol/L) for 0–72 hours. MTT assay was used to evaluate the inhibition effect of Celastrol on the growth of DU145 cells. Cell apoptosis was detected through both Annexin-V FITC/PI double-labeled cytometry and Hoechst 33258. Cell cycle regulation was examined by a propidium iodide method. Western blot and RT-PCR technologies were applied to assess the expression level of hERG in DU145 cells.Results.Celastrol presented striking growth inhibition and apoptosis induction potency on DU145 cellsin vitroin a time- and dose-dependent manner. The IC50value of Celastrol for 24 hours was 2.349 ± 0.213 μmol/L. Moreover, Celastrol induced DU145 cell apoptosis in a cell cycle-dependent manner, which means Celastrol could arrest DU145 cells in G0/G1phase; accordingly, cells in S phase decreased gradually and no obvious changes were found in G2/M phase cells. Through transmission electron microscope, apoptotic bodies containing nuclear fragments were found in Celastrol-treated DU145 cells. Overexpression of hERG channel was found in DU145 cells, while Celastrol could downregulate it at both protein and mRNA level in a dose-dependent manner (P<0.01).Conclusions.Celastrol exhibits its antiprostate cancer effects partially through the downregulation of the expression level of hERG channel in DU145 cells, suggesting that Celastrol may be a potential agent against prostate cancer with a mechanism of blocking the hERG channel.

scholarly journals ESTAT3 Inhibitor AG-490 Inhibits the Growth of Prostate Cancer by miR-503-5p Both In Vivo and In Vitro

2020 ◽  
Vol 19 ◽  
pp. 153303382094806
Author(s):  
Guangxing Tan ◽  
Lin Jiang ◽  
Gangqin Li ◽  
Kuan Bai
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Nude Mouse ◽  
Luciferase Reporter ◽  
Control Group ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Mouse Xenograft Model ◽  
Pc3 Cells ◽  
Du145 Cells

Objective: To explore the effect and the related mechanism of STAT3 inhibitor AG-490 on inhibiting the proliferation of prostate cancer cells. Methods: PC3 cells and DU145 cells were cultured stably and treated with AG-490 to detect the changes in the activity of PC3 cells and DU145 cells. Thirty 6-8 weeks male BALB/c nude mouse were randomly divided into a control group, a DMSO group, and an AG-490 group to detect differences in various indexes . Results: The overexpression of miR-503-5p depends on the activation of STAT3. After treatment with AG-490, The proliferation and invasion of PC3 cells and DU145 cells and the expression of miR-503-5p were all reduced. Luciferase reporter assay demonstrated that the target proteins of miR-503-5p include PDCD4, TIMP-3, and PTEN. After treatment with AG-490, the expression of PDCD4, TIMP-3, and PTEN in cells was significantly up-regulated. IL-6-induced overexpression of miR-503-5p and restored the expression of STAT3, demonstrating the correlation between STAT3 and miR-503-5p. AG-490 can inhibit tumor growth and induce tumor cell apoptosis in the PC3 BALB/c nude mouse xenograft model. Western blotting and immunohistochemical staining showed that the expression levels of STAT3, Ki67, Bcl-2 and MMP-2 in the AG-490 group were significantly reduced, and the expression of PDCD4, TIMP-3 and PTEN increased. Conclusion: AG-490 can inhibit the growth of prostate cancer cells in a miR-503-5p-dependent manner by targeting STAT3. AG-490 is expected to become a new candidate drug for the treatment of prostate cancer.

Silymarin Enriched Extract (Silybum marianum) Additive Effect on Doxorubicin-Mediated Cytotoxicity in PC-3 Prostate Cancer Cells

Planta Medica ◽  
2019 ◽  
Vol 85 (11/12) ◽  
pp. 997-1007 ◽  
Author(s):  
Katerina Gioti ◽  
Anastasia Papachristodoulou ◽  
Dimitra Benaki ◽  
Sophia Havaki ◽  
Apostolos Beloukas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Silybum Marianum ◽  
Altered Expression ◽  
Expression Levels ◽  
Branched Chain

AbstractSilymarin-enriched extract (SEE) is obtained from Silybum marianum (Asteraceae). Doxorubicin (DXR) is a widely used chemotherapeutical yet with severe side effects. The goal of the present study was to assess the pharmacologic effect of SEE and its bioactive components silibinin and silychristine when administrated alone or in combination with DXR in the human prostate cancer cells (PC-3). PC-3 cells were treated with SEE, silibinin (silybins A and B), silychristine, alone, and in combination with DXR, and cell proliferation was assessed by the MTT assay. Cell cycle, apoptosis, and autophagy rate were assessed by flow cytometry. Expression levels of autophagy-related genes were quantified by qRT-PCR, ELISA and western blot while transmission electron microscopy was performed to reveal autophagic structures. Finally, NMR spectrometry was used to identify specific metabolites related to autophagy. SEE inhibited PC-3 cell proliferation in a dose-dependent manner while the co-treatment (DXR-SEE) revealed an additive cytotoxic effect. Cell cycle, apoptosis, and autophagy variations were observed in addition to altered expression levels of autophagy related genes (LC3, p62, NBR1, Beclin1, ULK1, AMBRA1), while several modifications in autophagic structures were identified after DXR-SEE co-treatment. Furthermore, treated cells showed a different metabolic profile, with significant alterations in autophagy-related metabolites such as branched-chain amino acids. In conclusion, the DXR-SEE co-treatment provokes perturbations in the autophagic mechanism of prostate cancer cells (PC-3) compared to DXR treatment alone, causing an excessive cell death. These findings propose the putative use of SEE as an adjuvant cytotoxic agent.

scholarly journals Growth inhibition of androgen-responsive prostate cancer cells with brefeldin A targeting cell cycle and androgen receptor

2010 ◽  
Vol 17 (1) ◽  
pp. 5 ◽  
Author(s):  
Srinivas Rajamahanty ◽  
Catherine Alonzo ◽  
Shahrad Aynehchi ◽  
Muhammad Choudhury ◽  
Sensuke Konno
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Androgen Receptor ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Brefeldin A ◽  
Prostate Cancer Cells

scholarly journals Traditional Herbal Formula Taeeumjowi-Tang (TJ001) Inhibits p53-Mutant Prostate Cancer Cells Growth by Activating AMPK-Dependent Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Sooyeon Kang ◽  
Hyo In Kim ◽  
Yu-Jeong Choi ◽  
Seul Ki Lee ◽  
Ji Hye Kim ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Mutant P53 ◽  
Prostate Cancer Cells ◽  
Cycle Arrest ◽  
Du145 Cells

Dysregulated lipid metabolism is a prominent feature of prostate cancers (PCas); several enzymes involved in lipid accumulation are highly expressed. Here, we elucidated efficacy of TJ001, a traditional herbal decoction, in inhibiting de novo lipogenesis. TJ001 had significant cytotoxicity against DU145 but not PC3 and LNCaP cells and, similarly, TJ001 markedly AMPK phosphorylation only in DU145 cells. This was accompanied by the downregulation of phosphorylated-acetyl coenzyme A carboxylase (ACC) expression and sterol regulatory element-binding protein 1 (SREBP1) proteolytic cleavage, thereby inhibiting its role as a transcription factor to induce lipid biosynthesis. When Oil Red O staining was performed, it is reflected in the reduction of lipid droplets (LDs). TJ001 also induced G1/S cell cycle arrest via a cell cycle inhibitor (CKI) p21WAF1/CIP1 upregulation. Although p53 proteins remained unchanged, both cyclin E and cyclin D1 were decreased. Moreover, TJ001 suppressed the mammalian target of rapamycin (mTOR) signaling pathway. Generally, the prolonged G1/S phase arrest accompanies apoptosis, but TJ001 failed to work as a trigger apoptosis in DU145 cells. We showed that mutant p53 proteins were required for the survival of DU145 cells. In presence of TJ001, inhibition of endogenous mutant p53 by RNAi led to cell viability reduction and induction of the p-AMPK/AMPK ratio. In addition, it induced apoptotic cell death in DU145 cells. At the cellular level, induction of PARP, caspase-3, and caspase-9 cleavages was observed, and caspase-3 activity was increased in the p53 knockdown cells treated with TJ001. Taken together, we demonstrated that TJ001 inhibited cell growth in DU145 prostate cancer cells as indicated by blocking lipogenesis and induction in G1/S cell cycle arrest. In addition, we may provide an evidence that mutant p53 protein has potential role as an oncogenic action in DU145 cells. Collectively, the combination of mutant p53 targeting and TJ001 treatment resulted in decreased cell growth in DU145 cells.

scholarly journals Indole-3-carbinol (I3C) induced cell growth inhibition, G1 cell cycle arrest and apoptosis in prostate cancer cells

Oncogene ◽  
2001 ◽  
Vol 20 (23) ◽  
pp. 2927-2936 ◽  
Author(s):  
Sreenivasa R Chinni ◽  
Yiwei Li ◽  
Sunil Upadhyay ◽  
Prathima K Koppolu ◽  
Fazlul H Sarkar
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cell Growth Inhibition ◽  
Prostate Cancer Cells ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

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 Diarylpentanoid (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one) (MS13) Exhibits Anti-proliferative, Apoptosis Induction and Anti-migration Properties on Androgen-independent Human Prostate Cancer by Targeting Cell Cycle–Apoptosis and PI3K Signalling Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Nurul Azwa Abd Wahab ◽  
Faridah Abas ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Morphological Observation ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Anti Cancer ◽  
Cancer Activity ◽  
Androgen Independent

Diarylpentanoids exhibit a high degree of anti-cancer activity and stability in vitro over curcumin in prostate cancer cells. Hence, this study aims to investigate the effects of a diarylpentanoid, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13) on cytotoxicity, anti-proliferative, apoptosis-inducing, anti-migration properties, and the underlying molecular mechanisms on treated androgen-independent prostate cancer cells, DU 145 and PC-3. A cell viability assay has shown greater cytotoxicity effects of MS13-treated DU 145 cells (EC50 7.57 ± 0.2 µM) and PC-3 cells (EC50 7.80 ± 0.7 µM) compared to curcumin (EC50: DU 145; 34.25 ± 2.7 µM and PC-3; 27.77 ± 6.4 µM). In addition, MS13 exhibited significant anti-proliferative activity against AIPC cells compared to curcumin in a dose- and time-dependent manner. Morphological observation, increased caspase-3 activity, and reduced Bcl-2 protein levels in these cells indicated that MS13 induces apoptosis in a time- and dose-dependent. Moreover, MS13 effectively inhibited the migration of DU 145 and PC-3 cells. Our results suggest that cell cycle-apoptosis and PI3K pathways were the topmost significant pathways impacted by MS13 activity. Our findings suggest that MS13 may demonstrate the anti-cancer activity by modulating DEGs associated with the cell cycle-apoptosis and PI3K pathways, thus inhibiting cell proliferation and cell migration as well as inducing apoptosis in AIPC cells.

scholarly journals Anti-Cancer Effects of Paris Polyphylla Ethanol Extract by Inducing Cancer Cell Apoptosis and Cycle Arrest in Prostate Cancer Cells

2017 ◽  
Vol 11 (3) ◽  
pp. 144-150 ◽  
Author(s):  
Denglu Zhang ◽  
Kailin Li ◽  
Chao Sun ◽  
Guangshang Cao ◽  
Yuanfu Qi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Ethanol Extract ◽  
Prostate Cancer Cells ◽  
Cycle Arrest ◽  
Paris Polyphylla ◽  
Du145 Cells

Objective: To evaluate the potential anti-prostate cancer effects of Paris polyphylla ethanol extract (PPEE) and its underlying mechanisms. Materials and Methods: The anti-proliferation activity of PPEE was tested on PC3 and DU145 cells using Cell Counting Kit-8 assay. The pro-apoptotic and cell cycle arrest effects of PPEE were confirmed by flow cytometry. Apoptosis of prostate cancer cells was induced by PPEE through endogenous and exogenous pathways. A mouse xenograft model was used to examine its anti-prostate cancer effects in vivo. Results: We found that the IC50 of PPEE on PC3 cells was 3.98 µg/ml and the IC50 of PPEE on DU145 cells was 8 µg/ml. PPEE induced prostate cancer cell apoptosis in a concentration dependent manner, through endogenous and exogenous pathways. PPEE induced PC3 cell cycle arrest in G0/G1 and G2/M phases, while in DU145cell it induced cell arrest in the G0/G1 phase. PPEE inhibited the growth of prostate cancer cells in vivo. Conclusion: PPEE could inhibit prostate cancer growth in vitro and in vivo, induce apoptosis of prostate cancer cells, and cause cell cycle arrest, which laid the foundation for further research on the anti-tumor mechanism of PPEE.

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