scholarly journals Molecular basis of the anti-cancer effects of genistein isoflavone in LNCaP prostate cancer cells

2011 ◽  
Vol 1 (3) ◽  
pp. 91 ◽  
Author(s):  
K. Merchant ◽  
J. Kumi-Diaka ◽  
A. Rathinavelu ◽  
N. Esiobu ◽  
R. Zoeller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Side Effects ◽  
Cancer Cells ◽  
The United States ◽  
Dependent Manner ◽  
Apoptosis Induction ◽  
Prostate Cancer Cells ◽  
Expression Levels

Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic side effects to the patient. In this study, we investigated the effect of genistein isoflavone, a soy derivative, on expression levels of genes involved in these pathways. The mechanism of genistein-induced cell death was also investigated. The chemosensitivity of the LNCaP prostate cancer cells to genistein was investigated using ATP and MTS assays, and a caspase binding assay was used to determine apoptosis induction. Several molecular targets were determined using cDNA microarray and RT-PCR analysis.Results: The overall data revealed that genistein induces cell death in a time- and dose-dependent manner, and regulates expression levels of several genes involved in carcinogenesis and immunity. Several cell-cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin-dependent kinases. Various members of the Bcl-2 family of apoptotic proteins were also affected. The DefB1 and the HLA membrane receptor genes involved in immunogenicity were also up-regulated. Conclusion: The results indicate that genistein inhibits growth of the hormone-dependent prostate cancer cells, LNCaP, via apoptosis induction through regulation of some of the genes involved in carcinogenesis of many tumors, and immunogenicity. This study augments the potential phytotherapeutic and immunotherapeutic significance of genistein isoflavone. Key words: Genistein isoflavone, prostate cancer, expression of genes, phytotherapeutic adjuvant, immunotherapy and chemotherapy

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 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 FOXA1 knock-out via CRISPR/Cas9 altered Casp-9, Bax, CCND1, CDK4, and fibronectin expressions in LNCaP cells

2018 ◽  
Vol 243 (12) ◽  
pp. 990-994 ◽  
Author(s):  
Gulsah Albayrak ◽  
Ece Konac ◽  
Asiye Ugras Dikmen ◽  
Cenk Y Bilen
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Protein Expression ◽  
Cancer Cells ◽  
Drug Target ◽  
Molecular Subtypes ◽  
Prostate Cancer Cells ◽  
Knock Out ◽  
Expression Levels ◽  
Protein Expressions

Prostate cancer is one of the most common types of cancer in men and the leading cause of death in developed countries. With the aid of molecular and genetic profiling of cancers, cancer molecular subtypes are paving the way for tailored cancer therapy. FOXA1 has been identified as one of the seven molecular subtypes of prostate cancer. FOXA1 is involved in a variety of metabolic process such as glucose homeostasis and deregulation of its expression is crucial in prostate cancer progression. In this study, we investigated the effects of FOXA1 gene knock-out on the expression levels of various cancer cell metabolism and cell cycle-related protein expressions. FOXA1 gene was knocked-out by using CRISPR/Cas9 technique. While FOXA1 gene knock-out significantly altered Casp-9, Bax, CCND1, CDK4, and fibronectin protein expressions (P < 0.05, fold change: ∼40, 4.5, 2.5, 4.5, and 4, respectively), it did not affect the protein expression levels of Casp-3, Bcl-2, survivin, β-catenin, c-Myc, and GSK-3B. Knocking-out FOXA1 gene in androgen-dependent LNCaP prostate cancer cells inhibited CCND1 protein expression. Our pre-clinical results demonstrate the importance of FOXA1 as a drug target in the treatment of prostate cancer. Impact statement Knock-out studies offer a unique way of studying the function of genes especially for developmentally lethal genes. FOXA1 has prominent roles both in breast and prostate cancer pathogenesis due to its role in ER receptor signaling pathway. FOXA1 has also been identified as one of the seven molecular subtypes of primary prostate cancer. In the present study, we used an efficient gene knock-out method, CRISPR/Cas9, in order to investigate FOXA1 function on LNCaP prostate cancer cells in vitro. FOXA1 knock-out altered cell-cycle regulator CCND1 protein expression levels. Therefore, our results suggest that FOXA1 might be a plausible drug target for prostate cancer treatment.

scholarly journals Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Xiuhua Zhang ◽  
Minxiao Chen ◽  
Peng Zou ◽  
Karvannan Kanchana ◽  
Qiaoyou Weng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Er Stress ◽  
Cancer Cells ◽  
Human Prostate Cancer ◽  
Prostate Cancer Cells ◽  
Curcumin Analog ◽  
M Cell ◽  
Cycle Arrest

Physangulidine A, a Withanolide fromPhysalis angulata, Perturbs the Cell Cycle and Induces Cell Death by Apoptosis in Prostate Cancer Cells

2012 ◽  
Vol 76 (1) ◽  
pp. 2-7 ◽  
Author(s):  
E. Merit Reyes-Reyes ◽  
Zhuang Jin ◽  
Abraham J. Vaisberg ◽  
Gerald B. Hammond ◽  
Paula J. Bates
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cancer Cells ◽  
Prostate Cancer Cells

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.

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