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Keke Zhang, Fei Yan, Xiaoying Lei, Di Wei, Huanyu Lu, Zheng Zhu, An Xiang, Zichen Ye, Li Wang, Wanxiang Zheng, Xi'an Li, Jiarui Yuan, Zifan Lu, Jianlin Yuan
The androgen receptor (AR) has a crucial role in prostate cancer. RNA‑binding protein‑mediated post‑transcriptional regulation is important in the initiation and development of cancer. The present study attempted to elucidate the mutual association of AR and RNA‑binding protein quaking (QKI) in the development of prostate cancer. Dual‑luciferase reporter demonstrated that AR can positively regulate the expression of QKI in prostate cancer cell lines due to its effective transcription regulating function...
April 13, 2018: Molecular Medicine Reports
J Wu, H Sun, X Yang, X Sun
BACKGROUND: Androgen deprivation therapy (ADT) remains a standard treatment for advanced prostate cancers. However, recent studies revealed that while inhibiting the growth of certain types of prostate cancer cells, ADT promotes invasion. In the current study, we explored the effects of Nur77, an orphan nuclear receptor, on prostate cancer cell invasion following ADT. METHODS: Androgen receptor (AR) and Nur77 protein expression in patient tissues and cell lines were quantified via ELISA and western blot...
March 28, 2018: Clinical & Translational Oncology
WanYing Lin, Jie Luo, Yin Sun, ChangYi Lin, Gonghui Li, Yuanjie Niu, Chawnshang Chang
The androgen-deprivation therapy (ADT) to either reduce the androgen biosynthesis (for example, Abiraterone) or to prevent binding of androgen to the androgen receptor (AR), for example using Casodex or Enzalutamide, which may result in .decrease of the prostate cancer (PCa) cell growth, yet may also increase the PCa cell invasion. In contrast, the recently identified AR degradation enhancer ASC-J9® may function via degrading the AR protein to simultaneously suppress the PCa cell proliferation and invasion...
July 1, 2018: Cancer Letters
Felipe de Jesus Cortez, Phuong Nguyen, Charles Truillet, Boxue Tian, Kristopher M Kuchenbecker, Michael J Evans, Paul Webb, Matthew P Jacobson, Robert J Fletterick, Pamela M England
Resistance to clinical antiandrogens has plagued the evolution of effective therapeutics for advanced prostate cancer. As with the first-line therapeutic bicalutamide (Casodex), resistance to newer antiandrogens (enzalutamide, ARN-509) develops quickly in patients, despite the fact that these drugs have ∼10-fold better affinity for the androgen receptor than bicalutamide. Improving affinity alone is often not sufficient to prevent resistance, and alternative strategies are needed to improve antiandrogen efficacy...
December 15, 2017: ACS Chemical Biology
Ahmed Bulldan, Viveka Nand Malviya, Neha Upmanyu, Lutz Konrad, Georgios Scheiner-Bobis
ZIP9 is a Zn2+ transporter, testosterone receptor, and mediator of signaling events through G-proteins. Despite these pivotal properties, however, its physiological and pathophysiological significance has not yet been comprehensively addressed. Using a cell line that lacks the classical androgen receptor we show that ZIP9-mediated phosphorylation of Erk1/2, CREB, or ATF-1 and expression of claudin-5 and zonula occludens-1 by testosterone can be completely antagonized by bicalutamide (Casodex), an anti-androgen of significant clinical impact...
December 2017: Biochimica et Biophysica Acta
Changcheng Guo, Shuyuan Yeh, Yuanjie Niu, Gonghui Li, Junhua Zheng, Lei Li, Chawnshang Chang
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941...
July 1, 2017: Cancer Letters
Zheng Zhang, Bo Jin, Yaqiong Jin, Shengquan Huang, Xiaohua Niu, Zebin Mao, Dianqi Xin
Androgens (AR) play an important role in initiation and progression of prostate cancer. It has been shown that AR exert their effects mainly through the androgen-activated AR which binds to androgen response elements (AREs) in the regulatory regions of target genes to regulate the transcription of androgen-responsive genes, thus, identification of AR downstream target gene is critical to understand androgen function in prostate cancer. In this study, our results showed that androgen treatment of LNCaP cells induced PTTG1 expression, which was blocked by the androgen receptor antagonist, Casodex...
January 1, 2017: Experimental Cell Research
Richard Ottman, Jenna Levy, William E Grizzle, Ratna Chakrabarti
miR-17-92a cluster miRNAs are transcribed from a polycistronic transcription unit C13orf25 that generates six mature miRNAs, miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a that are overexpressed in lung and colon cancers. Here we show that the expression of miR-17-92a miRNAs are reduced in cancerous prostate tissues compared to uninvolved areas and also in aggressive prostate cancer cells. Restoration of expression of all members of miR-17-92a cluster showed, decreased expression of cell cycle regulatory proteins cyclin D1 and SSH1; and LIMK1 and FGD4 of RhoGTPase signaling pathway...
November 8, 2016: Oncotarget
Simeng Wen, Jing Tian, Yuanjie Niu, Lei Li, Shuyuan Yeh, Chawnshang Chang
Early studies suggested that prostate cancer (PCa) stem/progenitor (S/P) cells might play key roles to promote the tumor initiation and metastasis. Yet their linkage to the failure of androgen deprivation therapy (ADT), however, remains unclear. Here we demonstrated that the ADT with anti-androgens Casodex (also known as Bicalutamide) and Enzalutamide (also known as MDV3100), but not the newly identified AR degradation enhancer, ASC-J9(®), increased PCa S/P population, which might then lead to enhance the PCa cell invasion...
July 1, 2016: Cancer Letters
Simeng Wen, Yuanjie Niu, Soo Ok Lee, Shuyuan Yeh, Zhiqun Shang, Hengheng Gao, Yanjun Li, Fuju Chou, Chawnshang Chang
Fatty acid synthase (FASN) is the key enzyme for the control of fatty acid synthesis that contributes significantly to the prostate cancer (PCa) progression. It was reported that androgens were able to induce FASN expression in PCa, and addition of the anti-androgen Casodex might suppress the androgen-induced FASN expression. However, here we found androgen-deprivation-therapy (ADT) with anti-androgens Bicalutamide (Casodex) or Enzalutamide (MDV3100) had little effect to suppress FASN expression and FASN-mediated cell growth and invasion during the castration resistant stage when the androgen concentration is 1 nM DHT (dihydrotestosterone)...
December 2016: Molecular Carcinogenesis
Seung-Hee Kim, Ki-Hoan Nam, Kyung-A Hwang, Kyung-Chul Choi
The aim of the present study was to determine whether hexabromocyclododecane (HBCD) or 4-nonylphenol (NP) may induce prostatic cancer progression in LNCaP cells. Androgenic effects of HBCD and NP were examined in LNCaP prostate cancer cells expressing androgen receptors (ARs). HBCD and NP increased LNCaP cell viability similar to dihydrotestosterone (DHT) by MTT assay. This phenomenon was reversed by treatment with Casodex, an AR antagonist, suggesting that they act as xenoandrogens via AR signaling pathway...
April 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Xinyu Wu, Fangming Deng, Yirong Li, Garrett Daniels, Xinxin Du, Qinghu Ren, Jinhua Wang, Ling Hang Wang, Yang Yang, Valerio Zhang, David Zhang, Fei Ye, Jonathan Melamed, Marie E Monaco, Peng Lee
Increases in fatty acid metabolism have been demonstrated to promote the growth and survival of a variety of cancers, including prostate cancer (PCa). Here, we examine the expression and function of the fatty acid activating enzyme, long-chain fatty acyl-CoA synthetase 4 (ACSL4), in PCa. Ectopic expression of ACSL4 in ACSL4-negative PCa cells increases proliferation, migration and invasion, while ablation of ACSL4 in PCa cells expressing endogenous ACSL4 reduces cell proliferation, migration and invasion. The cell proliferative effects were observed both in vitro, as well as in vivo...
December 29, 2015: Oncotarget
Huiyan Wang, Lixia Zhang, Ying Fu, Fang Fang, Yong Jiang, Yuan Dong, Wenhe Zhu
BACKGROUND: Aberrant signaling pathways leads to cancer initiation and progression. Both Notch and PI3K/AKT signaling pathways are believed to be involved in prostate cancer. How the interaction between the two pathways contributes to prostate cancer progression to androgen independence is still elusive. METHODS: Prostate cancer cells were grown in RPMI 1,640 supplemented with 10% heat-inactivated fetal bovine serum (FBS) or 10% charcoal-stripped heat-inactivated fetal bovine serum (FCS), 1% penicillin-streptomycin in 75 cm2 polystyrene flasks, and maintained at 37 °C in a humidified atmosphere with 5% CO2 ...
February 2016: Prostate
Vidyavathi Reddy, Min Wu, Nicholas Ciavattone, Nathan McKenty, Mani Menon, Evelyn R Barrack, G Prem-Veer Reddy, Sahn-Ho Kim
Androgen receptor (AR) plays a role in maintaining telomere stability in prostate cancer cells, as AR inactivation induces telomere dysfunction within 3 h. Since telomere dysfunction in other systems is known to activate ATM (ataxia telangiectasia mutated)-mediated DNA damage response (DDR) signaling pathways, we investigated the role of ATM-mediated DDR signaling in AR-inactivated prostate cancer cells. Indeed, the induction of telomere dysfunction in cells treated with AR-antagonists (Casodex or MDV3100) or AR-siRNA was associated with a dramatic increase in phosphorylation (activation) of ATM and its downstream effector Chk2 and the presenceof phosphorylated ATM at telomeres, indicating activation of DDR signaling at telomeres...
October 16, 2015: Journal of Biological Chemistry
Chieh Huo, Yung-Hsi Kao, Chih-Pin Chuu
Bone metastasis is very common in prostate cancer (PCa) and causes severe pain. PC-3 is an androgen receptor (AR)-negative PCa cell line with high metastatic potential established from PCa bone metastasis. We observed that re-expression of AR, which is located in the cytoplasm in the absence of androgen, suppressed cell motility, migration, and invasion of PC-3 cells as determined by wound healing assay and transwell assay. Micro-Western Array and Western blotting analysis indicated that re-expression of AR increased APC, Akt2, Akt3, PI3K p85, phospho-PI3K p85 Tyr458, PI3K p85, and E-cadherin but decreased GSK-3β, phospho-GSK-3β Ser9, phospho-mTOR Ser2448, Skp2, NF-κB p50, Slug, N-cadherin, β-catenin, vimentin, MMP-9, and Snail...
December 1, 2015: Cancer Letters
Naoki Mizutani, Minami Inoue, Yukari Omori, Hiromi Ito, Keiko Tamiya-Koizumi, Akira Takagi, Tetsuhito Kojima, Mitsuhiro Nakamura, Soichiro Iwaki, Masahiro Nakatochi, Motoshi Suzuki, Yoshinori Nozawa, Takashi Murate
Acid ceramidase (ACDase) metabolizes ceramide to sphingosine, leading to sphingosine 1-phosphate production. Reportedly, ACDase has been upregulated in prostate cancer. However, its regulatory mechanism remains unclear. LNCaP (androgen-sensitive prostate cancer cell line) but not PC3 and DU-145, (androgen-unresponsive cell lines) exhibited the highest ACDase protein. Among three cell lines, ASAH1 mRNA level was not correlated with ACDase protein expression, and the 5'-promoter activity did not show androgen dependency, suggesting the post-transcriptional regulation of ACDase in LNCaP cells...
October 2015: Journal of Biochemistry
Qiang Dang, Lei Li, Hongjun Xie, Dalin He, Jiaqi Chen, Wenbing Song, Luke S Chang, Hong-Chiang Chang, Shuyuan Yeh, Chawnshang Chang
The recently developed anti-androgen enzalutamide also known as (MDV3100) has the advantage to prolong by 4.8 months the survival of castration resistant prostate cancer (CRPC) patients. However, the mechanisms behind the potential side effects involving the induction of the prostate cancer (PCa) neuroendocrine (NE) differentiation remain unclear. Here we found PCa cells could recruit more mast cells than normal prostate epithelial cells, and enzalutamide (or casodex) treatment could further increase such recruitment that resulted in promoting the PCa NE differentiation...
August 2015: Molecular Oncology
Fu-Chao Liu, See-Tong Pang, Yung-Fong Tsai, Irshad H Chaudry, Huang-Ping Yu
Casodex (bicalutamide), an androgen receptor antagonist, is used for the treatment of prostate cancer. Recent evidences show that Akt signaling pathway exerts organ-protective effects after injury. The aim of this study was to investigate whether Akt plays any role in the casodex-mediated attenuation of hepatic injury after trauma-hemorrhagic shock. Male Sprague-Dawley rats underwent trauma hemorrhage (mean blood pressure kept at approximately 35-40 mm Hg for 90 min), followed by fluid resuscitation. During resuscitation, a single dose of casodex (5 mg/kg, intravenous) with and without a phosphatidylinositol 3-kinase inhibitor wortmannin (1 mg/kg, intravenous), wortmannin or vehicle was administered...
May 2015: Shock
Alessandra Fiorio Pla, Alessia Brossa, Michela Bernardini, Tullio Genova, Guillaume Grolez, Arnaud Villers, Xavier Leroy, Natalia Prevarskaya, Dimitra Gkika, Benedetta Bussolati
BACKGROUND: Prostate cancer is the second leading cause of male cancer death in developed countries. Although the role of angiogenesis in its progression is well established, the efficacy of anti-angiogenic therapy is not clearly proved. Whether this could depend on differential responses between tumor and normal endothelial cells has not been tested. METHODS: We isolated and characterized three lines of endothelial cells from prostate cancer and we tested the effect of Sunitinib and Sorafenib, and the combined treatment with the anti-androgen Casodex, on their angiogenic functions...
December 12, 2014: BMC Cancer
Tao Wang, Shuiming Guo, Zhuo Liu, Licheng Wu, Mingchao Li, Jun Yang, Ruibao Chen, Xiaming Liu, Hua Xu, Shaoxin Cai, Hui Chen, Weiyong Li, Shaohua Xu, Liang Wang, Zhiquan Hu, Qianyuan Zhuang, Liping Wang, Kongming Wu, Jihong Liu, Zhangqun Ye, Jun-Yuan Ji, Chenguang Wang, Ke Chen
Castration resistance is a major obstacle to hormonal therapy for prostate cancer patients. Although androgen independence of prostate cancer growth is a known contributing factor to endocrine resistance, the mechanism of androgen receptor deregulation in endocrine resistance is still poorly understood. Herein, the CAMK2N1 was shown to contribute to the human prostate cancer cell growth and survival through AR-dependent signaling. Reduced expression of CAMK2N1 was correlated to recurrence-free survival of prostate cancer patients with high levels of AR expression in their tumor...
November 15, 2014: Oncotarget
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