scholarly journals In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues

2020 ◽  
Vol 13 (3) ◽  
pp. 47 ◽  
Author(s):  
Katarzyna B. Kaczor-Keller ◽  
Anna Pawlik ◽  
Jacek Scianowski ◽  
Agata Pacuła ◽  
Magdalena Obieziurska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cell ◽  
Biological Activities ◽  
Cytotoxic Action ◽  
Organoselenium Compounds ◽  
M Cell ◽  
Normal Prostate ◽  
Prostate Cell ◽  
Anticancer Mechanism

Scientific research has been underway for decades in order to develop an effective anticancer drug, and it has become crucial to find a novel and effective chemotherapeutics in the case of prostate cancer treatment. Ebselen derivatives have been shown to possess a variety of biological activities, including cytostatic and cytotoxic action against tumor cells. In this study, the cytotoxic effect and anticancer mechanism of action of two organoselenium compounds— (N-allyl-1,2-benzisoselenazol-3(2H)-one (N-allyl-BS) and N-(3-methylbutyl)-1,2-benzisoselenazol-3(2H)-one) (N-(3-mb)-BS)—were investigated on two phenotypically different prostate cancer cell lines DU 145 and PC-3. The influence of analyzed compounds on the viability parameter was also assessed on normal prostate cell line PNT1A. The results showed that both organoselenium compounds (OSCs) efficiently inhibited cancer cell proliferation, whereas normal PNT1A cells were less sensitive to the analazyed ebselen analouges. Both OSCs induced G2/M cell cycle arrest and prompted cell death through apoptosis. The detection of cleaved Poly (ADP-ribose) Polymerase (PARP) confirmed this. In addition, N-allyl-BS and N-(3-m)-b-BS increased the level of reactive oxygen species (ROS) formation, however only N-allyl-BS induced DNA damage. Based on our data, we assume that OSCs’ anticancer action can be associated with oxidative stress induction and inactivation of the Akt- dependent signalling pathway. In conclusion, our data demonstrate that ebselen derivatives showed strong cytotoxic efficiency towards prostate cancer cells and may be elucidated as a novel, potent anticancer agent.

scholarly journals Some Wild Edible Mushroom Anticancer Activity Against Prostate Cell Lines

Proceedings ◽  
2019 ◽  
Vol 40 (1) ◽  
pp. 40
Author(s):  
Hatice Bekci ◽  
Mustafa Cam ◽  
Ahmet Cumaoglu
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Anticancer Activities ◽  
Prostate Cancer Cell Lines ◽  
Prostate Cell

Prostate cancer is one of the cause of mortality and morbidity in men. High nutritional quality mushrooms have been consumed as food for a long time and Thanks to their bioactive components, they can be used in many fields such as pharmaceuticals, cosmetic products, dietary supplements and functional food production. The purpose of the research was to evaluate these derivatives against in vitro to obtain novel specific and effective anticancer agents against prostate cancer. In the study, Amanita caesarea, Sparassis crispa, Lepista nuda, Auricularia auricula, Tricholoma terreum and Lentinus tigrinus fungi were used. Anticancer activities of the compounds were evaluated in vitro by using MTT method against PC-3 and DU-143 (androgen-independent human prostate cancer cell lines) prostate cancer cell lines. Cisplatin was used as the positive sensitivity reference standard. The most effective among these fungus species biological activity against PC3 cancer cell line (IC50 = 327.34 µM), against DU-145 (IC50 = 459.19 µM).

Cerebellar Degeneration-Related Autoantigen 1 (CDR1) Gene Expression in Prostate Cancer Cell Lines

2014 ◽  
Vol 29 (3) ◽  
pp. 288-290 ◽  
Author(s):  
Michele Salemi ◽  
Filippo Fraggetta ◽  
Antonio Galia ◽  
Pietro Pepe ◽  
Laura Cimino ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Cerebellar Degeneration ◽  
Normal Prostate ◽  
Prostate Cell ◽  
Prostate Cell Line ◽  
Normal Prostate Cell

Prostate cancer (PCa) is the most frequent cancer among men in many developing countries, and the second leading cause of cancer-related death in men. A genetic component has been implicated in PCa onset and development. The cerebellar degeneration-related autoantigen 1 ( CDR1) gene, mapping in Xq26-q27.2, is expressed in cerebrum, cerebellum, heart, lung, liver, and kidney. In addition, CDR1 expression has been detected in neuroblastoma, renal carcinoma cell lines, and other cancer cell lines. In this study, we investigated the expression of the CDR1 gene in the LNCaP and PC-3 PCa cell lines, and in the PNT1A normal prostate cell line. CDR1 mRNA expression was evaluated by qRT-PCR. We found that the CDR1 gene was overexpressed in the LNCaP and PC-3 PCa cell lines as compared with the PNT1A normal prostate cell line. These data suggest that CDR1 could be a new biomarker for PCa identification.

scholarly journals USP16 regulates castration-resistant prostate cancer cell proliferation by deubiquitinating and stablizing c-Myc

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jianchao Ge ◽  
Wandong Yu ◽  
Junhong Li ◽  
Hangbin Ma ◽  
Pengyu Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Gene Signature ◽  
Cell Counting ◽  
Normal Prostate ◽  
Immunohistochemistry Staining ◽  
Myc Gene

Abstract Background c-Myc, a well-established oncogene, plays an important role in the initiation and progression of various cancers, including prostate cancer. However, its mechanism in cancer cell remains largely unknown and whether there exist a deubiquitinase targeting c-Myc also remains elusive. Methods Bioinformatic analysis and shRNA screening methods were used to identify potential deubiquitinases that correlate with c-Myc gene signature. Cell proliferation and viability were measured by Cell-Counting-Kit 8 and colony formation assays. A mouse xenograft model of PC3 cells was established to confirm the function of USP16 in vivo. The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays. Immunohistochemistry staining was performed to detect the expression of USP16, Ki67, and c-Myc in xenograft tissues and clinical tumour tissues. Furthermore, the correlation between USP16 and c-Myc was confirmed by RNA sequencing. Results Functional analyses identified USP16, known as a deubiquitinase, was strongly correlated with the c-Myc gene signature. Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo. Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption. Immunohistochemistry staining and RNA-seq tactics were further used to confirm the positive correlation between USP16 and c-Myc expression. Expression of USP16 in human PCa tissues was higher than that seen in normal prostate tissues and its high expression was found associated with poor prognosis. Conclusions USP16 serves as a novel deubiquitinase of c-Myc. Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo. USP16 regulates PCa cell proliferation by deubiquitinating and stabilizing c-Myc, making it a potential therapeutic candidate for the treatment of PCa.

USP2a is an oncogenic isopeptidase and a potential target in prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14522-14522
Author(s):  
C. Priolo ◽  
D. Tang ◽  
M. Brahmandam ◽  
B. Benassi ◽  
E. Sicinska ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Nude Mice ◽  
Fatty Acid Synthase ◽  
Chemotherapeutic Agents ◽  
Human Prostate ◽  
Wild Type ◽  
Normal Prostate ◽  
Prostate Cell

14522 Background: De-ubiquitinating enzymes (isopeptidases) remove ubiquitin side chains prior to degradation by the proteosome thus stabilizing their protein targets. We have identified a novel androgen regulated isopeptidase, USP2a, and demonstrated that it binds and prolongs the half-life of fatty acid synthase (FAS), a key enzyme in lipid metabolism of tumor cells. Methods: We determined whether USP2a has oncogenic properties in vitro and in vivo. Wild-type and catalytically inactive USP2a were introduced in immortalized normal prostate epithelial cells (AR-iPrECs). Clonogenicity assays and apoptosis induction by chemotherapeutic agents were performed on these cells. Anti-USP2a siRNA were transfected in normal and transformed (LNCaP, DU145 and PC-3) prostate cell lines. Oncogenicity in vivo was shown by s.c. injection of NIH3T3-USP2a cells in nude mice. Furthermore, USP2a mRNA expression and gene microarrays were tested in 52 human prostate adenocarcinomas. Results: Wild-type USP2a overexpression in AR-iPrEC cells resulted in a significant increase in number and size of colonies compared to those obtained in parental cells. Growth in soft agar was significantly enhanced as well. Silencing of USP2a in LNCAP and DU145 cells resulted in a strong apoptotic effect, evaluated by FACS analysis and cleaved-PARP expression. The role of this isopeptidase in apoptosis regulation was confirmed on AR-iPrEC-USP2a cells, that showed resistance to apoptosis induced by cisplatin and taxol. Importantly, USP2a overexpression was able to transform NIH3T3 cells, generating greater than or equal to 0.5 cm subcutaneous tumors in 12/12 nude mice within 3 weeks, while none of the negative controls grew. USP2a mRNA was overexpressed in 39% of human prostate cancers, showing 1.6–104 (median 5.48) fold induction relative to normal tissues by qRT-PCR. Gene expression profiling of the same tumors revealed specific signatures in USP2a-overexpressing tumors. Conclusions: Our results demonstrate that USP2a behaves as an oncogene in vitro and in vivo and is overexpressed in organ-confined prostate cancer. These data strongly suggest that this isopeptidase is a potential drug target in prostate cancer. [Table: see text]

Biological role of cytoplasmic transducin beta like related protein 1-induced proliferation and tumorigenicity in prostate cancer

2018 ◽  
Vol 6 (3) ◽  
pp. 223-235
Author(s):  
Shu-Peng Zheng ◽  
Xiang Feng
Keyword(s):  
Prostate Cancer ◽  
Clinical Stage ◽  
Immunohistochemical Analysis ◽  
Related Protein ◽  
Normal Prostate ◽  
Tissue Samples ◽  
Prostate Cell

Androgen receptor mediated transcription and function in prostate cancer and critical for prostate cell growth and gland differentiation. Transducin beta like related protein 1 (TBLR1) primarily localizes in the nucleus in benign prostate tissue and is significantly reduced in prostate cancer. The objective of this study is investigated the role of cytoplasmic TBLR1in prostate cancer. Real-time PCR, Western blotting and immunocytochemistry were used to evaluate Transducin beta like related protein 1 (TBLR1) expression in prostate cancer cell lines and normal prostate cells, tissue samples and adjacent nontumor tissues, and in 142 paraffin-embedded specimens. Immunohistochemical analysis revealed high expression of TBLR1 in 89 of 214 paraffin-embedded archival prostate cancer. The expression level of TBLR1 was significantly increased in prostate cancer both in vivo and in vitro and correlated with clinical stage (P<0.05) and metastasis (P<0.001). Over all the study showed that the TBLR1 plays a key role in the development of prostate cancer cells and TBLR1 may be prognostic marker and a potential therapeutic target in the treatment human prostate cancer.

Procyanidin B3, an inhibitor of histone acetyltransferase, enhances the action of antagonist for prostate cancer cells via inhibition of p300-dependent acetylation of androgen receptor

2010 ◽  
Vol 433 (1) ◽  
pp. 235-244 ◽  
Author(s):  
Kyung-Chul Choi ◽  
SiYong Park ◽  
Beom Jin Lim ◽  
Ah-Reum Sung ◽  
Yoo-Hyun Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cell Growth ◽  
Cancer Cell ◽  
Histone Acetyltransferase ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth ◽  
Prostate Cell

Increasing evidence suggests that AR (androgen receptor) acetylation is critical for prostate cancer cell growth. In the present study, we identified Pro-B3 (procyanidin B3) as a specific HAT (histone acetyltransferase) inhibitor. Pro-B3 selectively inhibited the activity of HATs, but not other epigenetic enzymes. Pro-B3 substantially inhibited the p300-mediated AR acetylation, both in vitro and in vivo. Pro-B3 inhibited both p300-dependent and agonist-induced AR transcription. We demonstrate that the p300-mediated AR acetylation is critical for the hormone responsiveness of AR. Interestingly, B3 treatment efficiently enhanced the antagonist activity of flutamide through suppression of p300 HAT activity, demonstrating that relative p300 activity is critical for the antagonist action. Finally, Pro-B3 treatment inhibited acetylation-dependent prostate cell proliferation and expression of cell-cycle control genes, subsequently increasing cell death, indicating the functional importance of AR acetylation for prostate cancer cell growth.

scholarly journals USP16 Regulates Castration-Resistant Prostate Cancer Cell Proliferation by Deubiquitinating and Stablizing c-Myc

2020 ◽  
Author(s):  
Jianchao Ge ◽  
Wandong Yu ◽  
Junhong Li ◽  
Hangbin Ma ◽  
Pengyu Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Gene Signature ◽  
Cell Counting ◽  
Normal Prostate ◽  
Immunohistochemistry Staining ◽  
Myc Gene

Abstract Backgroundc-Myc, a well-established oncogene, plays an important role in the initiation and progression of various cancers, including prostate cancer. However, its mechanism in cancer cell remains largely unknown and whether there exist a deubiquitinase targeting c-Myc also remains elusive.MethodsBioinformatic analysis and shRNA screening methods were used to identify potential deubiquitinases that correlate with c-Myc gene signature. Cell proliferation and viability were measured by Cell-Counting-Kit 8 and colony formation assays. A mouse xenograft model of PC3 cells was established to confirm the function of USP16 in vivo. The interaction between USP16 and c-Myc protein was assessed by co-immunoprecipitation and protein co-localization assays. Immunohistochemistry staining was performed to detect the expression of USP16, Ki67, and c-Myc in xenograft tissues and clinical tumour tissues. Furthermore, the correlation between USP16 and c-Myc was confirmed by RNA sequencing.ResultsFunctional analyses identified USP16, known as a deubiquitinase, was strongly correlated with the c-Myc gene signature. Depletion of USP16 was shown to significantly suppress the growth of PCa cells both in vitro and in vivo. Co-immunoprecipitation and ubiquitination assays confirmed that USP16 served as a novel deubiquitinase of c-Myc and overexpression of c-Myc significantly rescued the effects of USP16 disruption. Immunohistochemistry staining and RNA-seq tactics were further used to confirm the positive correlation between USP16 and c-Myc expression. Expression of USP16 in human PCa tissues was higher than that seen in normal prostate tissues and its high expression was found associated with poor prognosis.ConclusionsUSP16 serves as a novel deubiquitinase of c-Myc. Downregulation of USP16 markedly suppressed PCa cell growth both in vitro and in vivo. USP16 regulates PCa cell proliferation by deubiquitinating and stabilizing c-Myc, making it a potential therapeutic candidate for the treatment of PCa.

794: Valproic Acid Inhibits Prostate Cancer Cell Growth in Vitro and in Vivo

2006 ◽  
Vol 175 (4S) ◽  
pp. 257-257
Author(s):  
Jennifer Sung ◽  
Qinghua Xia ◽  
Wasim Chowdhury ◽  
Shabana Shabbeer ◽  
Michael Carducci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Valproic Acid ◽  
Cell Growth ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Growth

Influence of New Synthetic Xanthones on the Proliferation and Migration Potential of Cancer Cell Lines In Vitro

2020 ◽  
Vol 19 (16) ◽  
pp. 1949-1965 ◽  
Author(s):  
Natalia Szkaradek ◽  
Daniel Sypniewski ◽  
Dorota Żelaszczyk ◽  
Sabina Gałka ◽  
Paulina Borzdziłowska ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Higher Plants ◽  
Biological Activities ◽  
Human Tumor ◽  
Plant Metabolites ◽  
Xtt Assay ◽  
Treatment Protocols

Background: Natural plant metabolites and their semisynthetic derivatives have been used for years in cancer therapy. Xanthones are oxygenated heterocyclic compounds produced as secondary metabolites by higher plants, fungi or lichens. Xanthone core may serve as a template in the synthesis of many derivatives that have broad biological activities. Objective: This study synthesized a series of 17 new xanthones, and their anticancer potential was also evaluated. Methods: The anticancer potential was evaluated in vitro using a highly invasive T24 cancer cell line. Direct cytotoxic effects of the xanthones were established by IC50 estimation based on XTT assay. Results: 5 compounds of the total 17 showed significant cytotoxicity toward the studied cancer cultures and were submitted to further detailed analysis, including studies examining their influence on gelatinase A and B expression, as well as on the cancer cells migration and adhesion to an extracellular matrix. These analyses were carried out on five human tumor cell lines: A2780 (ovarian cancer), A549 (lung cancer), HeLa (cervical cancer), Hep G2 (liver cancer), and T24 (urinary bladder cancer). All the compounds, especially 4, showed promising anticancer activity: they exhibited significant cytotoxicity towards all the evaluated cell lines, including MCF-7 breast cancer, and hindered migration-motility activity of cancer cells demonstrating more potent activity than α-mangostin which served as a reference xanthone. Conclusion: These results suggest that our xanthone derivatives may be further analyzed in order to include them in cancer treatment protocols.

scholarly journals Phenotypic Analysis of Mice Lacking the Tmprss2-Encoded Protease

2006 ◽  
Vol 26 (3) ◽  
pp. 965-975 ◽  
Author(s):  
Tom S. Kim ◽  
Cynthia Heinlein ◽  
Robert C. Hackman ◽  
Peter S. Nelson
Keyword(s):  
Serine Protease ◽  
Serine Proteases ◽  
Biological Activities ◽  
Type Ii ◽  
Phenotypic Analysis ◽  
Normal Prostate ◽  
Prostate Hyperplasia ◽  
Transmembrane Serine Protease

ABSTRACT Tmprss2 encodes an androgen-regulated type II transmembrane serine protease (TTSP) expressed highly in normal prostate epithelium and has been implicated in prostate carcinogenesis. Although in vitro studies suggest protease-activated receptor 2 may be a substrate for TMPRSS2, the in vivo biological activities of TMPRSS2 remain unknown. We generated Tmprss2 −/− mice by disrupting the serine protease domain through homologous recombination. Compared to wild-type littermates, Tmprss2 −/− mice developed normally, survived to adulthood with no differences in protein levels of prostatic secretions, and exhibited no discernible abnormalities in organ histology or function. Loss of TMPRSS2 serine protease activity did not influence fertility, reduce survival, result in prostate hyperplasia or carcinoma, or alter prostatic luminal epithelial cell regrowth following castration and androgen replacement. Lack of an observable phenotype in Tmprss2 −/− mice was not due to transcriptional compensation by closely related Tmprss2 homologs. We conclude that the lack of a discernible phenotype in Tmprss2 −/− mice suggests functional redundancy involving one or more of the type II transmembrane serine protease family members or other serine proteases. Alternatively, TMPRSS2 may contribute a specialized but nonvital function that is apparent only in the context of stress, disease, or other systemic perturbation.

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