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P53 and pc3

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...
September 19, 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, M 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...
July 19, 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...
July 19, 2016: 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
Wei Zhang, Bin Yi, Chao Wang, Dongquan Chen, Sejong Bae, Shi Wei, Rong-Jun Guo, Changming Lu, Lisa L H Nguyen, Wei-Hsiung Yang, James W Lillard, Xingyi Zhang, Lizhong Wang, Runhua Liu
PURPOSE: In prostate cancer cells, there is CD24-dependent inactivation of mutant p53, but the mechanism and its significance remain largely unknown. Here, we validated this observation and explored the therapeutic potential of targeting CD24 in TP53 mutant prostate cancer cells. EXPERIMENTAL DESIGN: Overall, 553 prostate cancers (522 formalin-fixed paraffin-embedded and 31 frozen tissues) were assessed for protein or mRNA expression of CD24 and TP53 The effects of CD24 on p53-dependent transcriptional regulation, cancer cell growth, the cell cycle, apoptosis, and mutant p53 restoration were also determined...
May 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Min-Chi Yang, Ru-Wei Lin, Shih-Bo Huang, Shin-Yuan Huang, Wen-Jie Chen, Shiaw Wang, Yi-Ren Hong, Chihuei Wang
Doxorubicin and other anthracycline compounds exert their anti-cancer effects by causing DNA damage and initiating cell cycle arrest in cancer cells, followed by apoptosis. DNA damage generally activates a p53-mediated pathway to initiate apoptosis by increasing the level of the BH3-only protein, Puma. However, p53-mediated apoptosis in response to DNA damage has not yet been validated in prostate cancers. In the current study, we used LNCaP and PC3 prostate cancer cells, representing wild type p53 and a p53-null model, to determine if DNA damage activates p53-mediated apoptosis in prostate cancers...
2016: Cell Cycle
Chunqi Hu, Yali Gao, Wenting Du
In this in vitro study, a series of novel pyrazole derivatives were designed, synthesized, and evaluated against five human cancer cell lines (PC3, A549, HL60, HCT116, and SW620) for their antiproliferative and p53-MDM2 binding inhibitory activities. Although biological evaluations showed that this series of compounds possessed weak p53-MDM2 inhibitory activities, most of them displayed moderate to potent antiproliferative activities against the tested cells lines. Compound 11c exhibited the best potency for MDM2 (FP-IC50 = 29...
May 2016: Chemical Biology & Drug Design
Elsayed I Salim, Afaf D Abd El-Magid, Khalid M Farara, Dina S M Maria
It has been shown previously that nutritional supplements rich in polyphenolic compounds play a significant role in prostate cancer chemoprevention. Propolis is a natural, resinous hive product that has several pharmacological activities including antimicrobial, antioxidant, anti-inflammatory, and antitumoral activities. The aim of this study was to compare the cytotoxic, antioxidant and antitumoral activities of an ethanolic extract of Egyptian propolis (EEP) in vitro with an established chemotherapeutic drug such as doxorubicin (DOX), and the effects of their combination against the PC3 human prostate cancer cell line...
2015: Asian Pacific Journal of Cancer Prevention: APJCP
Eda Acikgoz, Ummu Guven, Fahriye Duzagac, Ruchan Uslu, Mikail Kara, Burak Cem Soner, Gulperi Oktem
Trabectedin (Yondelis, ET-743) is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs). Cluster of differentiation (CD) 133+high/CD44+high prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry...
2015: PloS One
N Chi, Z Z Yun, Z H Tan, X Z Li, B T B G Chen, J Liu, L B Xu, K W Ma, S X Li, J F Liu, C X Liu
Prostate cancer cells were transfected with plasmids [empty plasmids, wild-type pcDNA3.1-p53 (V/V), mutant type pcDNA3.1- p53 (G/G)] to analyze the effect of p53 gene polymorphisms on the proliferation, cycle, and apoptosis of prostatic cancer cells. Empty plasmids containing wild-type pcDNA3.1-p53 (V/V) and mutant type pcDNA3.1- p53 (G/G) were used to transfect PC3 and LNCaP cells, respectively. Cell proliferation was detected at 0, 24, 48, and 72 h using the MTT method. Cells were collected at 24 and 72 h...
2015: Genetics and Molecular Research: GMR
Jianxu Zhang, Di Wu, Zhen Xing, Shaojun Liang, Haobo Han, Hui Shi, Yan Zhang, Yan Yang, Quanshun Li
In this paper, N-isopropylacrylamide-modified polyethylenimine (PEN) was constructed through Michael addition and employed as a carrier to achieve the p53 gene delivery, using HeLa (p53wt) and PC-3 cells (p53null) as models. After PEN-mediated p53 transfection, expression level of p53 in HeLa and PC3 cells was up-regulated at both mRNA and protein levels. Due to the exogenous p53 expression, the inhibition of cell proliferation was observed through MTT analysis, attributing to the activation of apoptosis and cell cycle arrest...
May 1, 2015: Colloids and Surfaces. B, Biointerfaces
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