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P53 and pc3

Saswati Banerjee, Santosh K Singh, Indrajit Chowdhury, Rajesh Singh
Docetaxel is the most commonly used chemotherapeutic agent to target androgen signaling in metastatic prostate cancer (PCa); however, prolonged treatment with docetaxel results in drug-resistant cancer cells. Combination therapies have the potential of increasing the effectiveness of drug treatment as well as decreasing the side effects. Curcumin is a nontoxic organic compound with multifaceted chemopreventive potential. In this study, we evaluated whether curcumin can reinforce the effect of docetaxel on PCa cells...
March 1, 2017: Frontiers in Bioscience (Elite Edition)
Laura Muñoz-Moreno, Ana M Bajo, Juan C Prieto, María J Carmena
The involvement of growth hormone-releasing hormone (GHRH) in several relevant processes that contribute to prostate cancer progression was analyzed. Firstly, we evaluated GHRH effects on cell proliferation and adhesion in human cancer prostate cell lines, LNCaP and PC3, by using specific assays (BrdU incorporation and collagen adhesion). The expression levels of the main marker molecules of these processes were measured by RT-PCR, Western blotting and zymography assays. GHRH increased both cell proliferation and proliferating cell nuclear antigen (PCNA) levels in LNCaP cells and in PC3 cells; however, such a rise was faster in the PC3 cells that represent the most aggressive stage of prostate cancer...
February 11, 2017: Molecular and Cellular Endocrinology
Rodrigo E Tamura, Aline Hunger, Denise Fernandes, Francisco Laurindo, Eugenia Costanzi-Strauss, Bryan E Strauss
Previously, we developed an adenoviral vector, Ad-PG, where transgene expression is regulated by a p53-responsive promoter. When used to transfer the p53 cDNA, a positive feedback mechanism is established. Here we perform a critical comparison between Ad-PGp53 and AdRGD-PGp53, where the RGD motif was incorporated in the adenoviral fiber protein. AdRGD-PGp53 provided superior transgene expression levels and resulted in the killing of prostate carcinoma cell lines DU145 and PC3. In vitro, this effect was associated with increased production of cytoplasmic and mitochondrial oxidants, DNA damage as revealed by detection of phosphorylated H2AX as well as cell death consistent with apoptosis...
February 9, 2017: Human Gene Therapy
Annie Rochette, Nadia Boufaied, Eleonora Scarlata, Lucie Hamel, Fadi Brimo, Hayley C Whitaker, Antonio Ramos-Montoya, David E Neal, Alice Dragomir, Armen Aprikian, Simone Chevalier, Axel A Thomson
BACKGROUND: Prostate cancer shows considerable heterogeneity in disease progression and we propose that markers expressed in tumour stroma may be reliable predictors of aggressive tumour subtypes. METHODS: We have used Kaplan-Meier, univariate and multivariate analysis to correlate the expression of Asporin (ASPN) mRNA and protein with prostate cancer progression in independent cohorts. We used immunohistochemistry and H scoring to document stromal localisation of ASPN in a tissue microarray and mouse prostate cancer model, and correlated expression with reactive stroma, defined using Masson Trichrome staining...
February 2, 2017: British Journal of Cancer
Jie Zhou, Jin-Hong Feng, Lei Fang
A novel monoterpenoid indole alkaloid with unprecedented 6/5/6/4/6 fused rings, khasuanine A (1), was isolated from the roots of Melodinus khasianus. The structure was determined by extensive analysis of its HR-MS, 1D-, and 2D-NMR spectra. Khasuanine A markedly inhibited the proliferation of PC3 cell with IC50 value of 0.45μM. Further study showed that khasuanine A was able to induce the apoptosis of PC3 cells by activation of caspase 3 and p53, and by inhibition of Bcl-2.
January 6, 2017: Bioorganic & Medicinal Chemistry Letters
Suat Erdogan, Kader Turkekul, Rıza Serttas, Zeynep Erdogan
Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44(+) PCa stem cell growth and migration...
January 17, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yeqing Huang, Xiangyu Zou, Xiaowen Zhang, Feng Wang, Weidong Zhu, Guangyuan Zhang, Jun Xiao, Ming Chen
BACKGROUND: Magnolin is the most active ingredient in the herb Magnolia fargesii, which has been traditionally used in oriental medicine to treat headaches and nasal congestion. Recent researches demonstrate that Magnolin inhibits cancer cell migration and invasion. MATERIALS AND METHODS: This study used cell culture and the BALB/c nu/nu mouse xenograft model to investigate whether or not magnolin can inhibit the growth of PC3 and Du145 prostate cancer cells. MTT assay and flow cytometry were performed to estimate the proliferation, cycle, and apoptosis of the cells in vitro...
March 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Annelies Gonnissen, Sofie Isebaert, Chad M McKee, Rüveyda Dok, Karin Haustermans, Ruth J Muschel
Limited data exists regarding the combination of Hedgehog signaling (Hh) inhibition and radiotherapy, even though there are several indications that this might be a promising treatment strategy. In this study, we evaluated the combination of two Hh inhibitors, the SMO inhibitor GDC-0449 and the GLI inhibitor GANT61 with radiotherapy in different prostate cancer (PCa) models. In vitro, GANT61 was able to sensitize 22Rv1 PCa cells but not PC3 and DU145 PCa cells. The lack of radiosensitization in the latter cell lines was shown to be dependent on the presence of mutated p53...
October 5, 2016: Oncotarget
Suman Kumar Tripathy, Umasankar De, Niranjan Dehury, Paltan Laha, Manas Kumar Panda, Hyung Sik Kim, Srikanta Patra
Six mononuclear Ir complexes (1-6) using polypyridyl-pyrazine based ligands (L1 and L2) and {[cp*IrCl(μ-Cl)]2 and [(ppy)2Ir(μ-Cl)]2} precursors have been synthesised and characterised. Complexes 1-5 have shown potent anticancer activity against various human cancer cell lines (MCF-7, LNCap, Ishikawa, DU145, PC3 and SKOV3) while complex 6 is found to be inactive. Flow cytometry studies have established that cellular accumulation of the complexes lies in the order 2 > 1 > 5 > 4 > 3 > 6 which is in accordance with their observed cytotoxicity...
September 27, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Rodrigo Esaki Tamura, Rafael Bento da Silva Soares, Eugenia Costanzi-Strauss, Bryan E Strauss
Alternative treatments for cancer using gene therapy approaches have shown promising results and some have even reached the marketplace. Even so, additional improvements are needed, such as employing a strategically chosen promoter to drive expression of the transgene in the target cell. Previously, we described viral vectors where high-level transgene expression was achieved using a p53-responsive promoter. Here we present an adenoviral vector (AdPGp53) where p53 is employed to regulate its own expression and which outperforms a traditional vector when tested in a model of gene therapy for prostate cancer...
December 2016: Cancer Biology & Therapy
Whasun Lim, Sunwoo Park, Fuller W Bazer, Gwonhwa Song
Prostate cancer is the most common cancer in men and the second most common cause of cancer-related deaths in men. Although various drugs targeting the androgen receptor are normally used, the patients frequently undergo recurrence of the disease. To overcome these limitations, natural compounds have been researched for evidence that they suppress progression and metastasis of various cancer cells. In the present study, we investigated effects of naringenin, a natural anti-oxidant flavonoid derived from citrus, on prostate cancer cells (PC3 and LNCaP)...
September 8, 2016: Journal of Cellular Biochemistry
Shravan Kumar Komaragiri, Dhanushka H Bostanthirige, Derrick J Morton, Divya Patel, Jugal Joshi, Sunil Upadhyay, Jaideep Chaudhary
Deregulation of tumor suppressor genes is associated with tumorigenesis and the development of cancer. In prostate cancer, ID4 is epigenetically silenced and acts as a tumor suppressor. In normal prostate epithelial cells, ID4 collaborates with androgen receptor (AR) and p53 to exert its tumor suppressor activity. Previous studies have shown that ID4 promotes tumor suppressive function of AR whereas loss of ID4 results in tumor promoter activity of AR. Previous study from our lab showed that ectopic ID4 expression in DU145 attenuates proliferation and promotes AR expression suggesting that ID4 dependent AR activity is tumor suppressive...
September 9, 2016: Biochemical and Biophysical Research Communications
Laura Muñoz-Moreno, Maria Isabel Arenas, María J Carmena, Andrew V Schally, Manuel Sánchez-Chapado, Juan C Prieto, Ana M Bajo
Growth hormone-releasing hormone (GHRH) and its receptors have been implicated in the progression of various tumors. In vitro and in vivo studies have demonstrated that GHRH antagonists inhibit the growth of several cancers. GHRH antagonists, JMR-132 and JV-1-38 inhibit the growth of androgen-independent prostate tumors. Here we investigated the involvement of GHRH antagonists in proliferative and apoptotic processes. We used non-tumoral RWPE-1 and tumoral LNCaP and PC3 human prostatic epithelial cells, as well as an experimental model of human tumor PC3 cells...
August 9, 2016: Oncotarget
Whasun Lim, Muhah Jeong, Fuller W Bazer, Gwonhwa Song
Coumestrol is the one of the major phytoestrogens which is abundant in soybeans, legumes, brussel sprouts, and spinach. The beneficial effects of coumestrol are well known in various biological processes including; neuroprotective effects on the nervous system, function of the female reproductive system, anti-bacterial properties, and anti-cancer effects. Although the anti-tumor activity of coumestrol has been demonstrated for ovarian, breast, lung, and cervical cancers, little is known of its effects on prostate cancer...
April 2017: Journal of Cellular Physiology
I Postiglione, F Barra, S M Aloj, G Palumbo
OBJECTIVES: In spite of high sensitivity of A549 cells (p53(+/+) ) to lethal effects of photodynamic therapy with 5-aminolaevulinic acid (5-ALA/PDT), DNA damage was observed only in H1299 cells (p53(-/-) ), suggesting that p53 may exert a protective effect. Studies on human colon adenocarcinoma cell lines HCT-116, and their cognate knockouts for p53, were not entirely consistent with the assumption above. Exploring alternative explanations for such conflicting behaviour, we observed that expression of the ATP-binding cassette G2 (ABCG2), a regulator of cell component efflux, had important effects on PDT-generated DNA injury in PC3 cells (prostate) which are p53(-/-) and positive for ABCG2...
August 2016: Cell Proliferation
Ok Ran Choi, Min Sook Ryu, In Kyoung Lim
Cellular senescence and apoptosis can be regulated by p53 activity, although the underlying mechanism of the switch between the two events remains largely unknown. Cells exposed to cancer chemotherapy can escape to senescence phenotype rather than undergoing apoptosis. By employing adenoviral transduction of p53 or TIS21 genes, we observed shifting of p53 induced-senescence to apoptosis in EJ bladder cancer cells, which express H-RasV12 and mutant p53; transduction of p53 increased H-RasV12 expression along with senescence phenotypes, whereas coexpression with TIS21 (p53+TIS21) induced cell death rather than senescence...
September 2016: Cellular Signalling
Annelies Suetens, Katrien Konings, Marjan Moreels, Roel Quintens, Mieke Verslegers, Els Soors, Kevin Tabury, Vincent Grégoire, Sarah Baatout
The use of charged-particle beams, such as carbon ions, is becoming a more and more attractive treatment option for cancer therapy. Given the precise absorbed dose-localization and an increased biological effectiveness, this form of therapy is much more advantageous compared to conventional radiotherapy, and is currently being used for treatment of specific cancer types. The high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited...
2016: Frontiers in Oncology
Ziga Ude, Isolda Romero-Canelón, Brendan Twamley, Deirdre Fitzgerald Hughes, Peter J Sadler, Celine J Marmion
7-(4-(Decanoyl)piperazin-1-yl)-ciprofloxacin, CipA, (1) which is an analogue of the antibiotic ciprofloxacin, and its ruthenium(II) complex [Ru(η(6)-p-cymene)(CipA-H)Cl], (2) have been synthesised and the x-ray crystal structures of 1·1.3H2O·0.6CH3OH and 2·CH3OH·0.5H2O determined. The complex adopts a typical pseudo-octahedral 'piano-stool' geometry, with Ru(II) π-bonded to the p-cymene ring and σ-bonded to a chloride and two oxygen atoms of the chelated fluoroquinolone ligand. The complex is highly cytotoxic in the low μM range and is as potent as the clinical drug cisplatin against the human cancer cell lines A2780, A549, HCT116, and PC3...
July 2016: Journal of Inorganic Biochemistry
Lei Jia, Jun Xu, Xiaolei Zhao, Shanshan Shen, Tao Zhou, Zhouqing Xu, Taofeng Zhu, Ruhua Chen, Tieliang Ma, Jing Xie, Kun Dong, Jiancui Huang
Three ternary copper (II) complexes containing 1,10-phenanthroline (phen, 1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq, 2) and dipyrido[3,2-a:2',3'-c]phenazine (dppz, 3), with the formulation [Cu2(NCL)2(H4PASP)]·4.5H2O (1-3) (where NCL=the diimine coligand, H4PASP=N,N'-(p-xylylene)di-2-aminosuccinic acid), were isolated and characterized. The binding of these complexes with calf thymus DNA was studied using UV-visible absorption titration, emission, and circular dichroism spectroscopy, among other methods. The changes in physicochemical properties that occurred upon binding of these complexes with DNA indicate that binding occurs primarily through intercalative interactions...
June 2016: Journal of Inorganic Biochemistry
Rie Amamoto, Takeshi Uchiumi, Mikako Yagi, Keisuke Monji, YooHyun Song, Yoshinao Oda, Masaki Shiota, Akira Yokomizo, Seiji Naito, Dongchon Kang
BACKGROUND: Mitochondria play crucial roles in cell signaling events, interorganellar communication, aging, cell proliferation and apoptosis, and mitochondrial impairment has been shown to accelerate or modulate cancer progression. Ubiquitous mitochondrial creatine kinase (uMtCK) is predominantly localized in the intermembrane space of mitochondria and catalyzes the reversible exchange of high-energy phosphate between adenosine tri-phosphate (ATP) and phosphocreatine. However, little is known about its expression and function in human prostate cancer progression...
2016: Journal of Cancer
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