Dihydrotestosterone enhances castration-resistant prostate cancer cell proliferation through STAT5 activation via glucocorticoid receptor pathway

The Prostate ◽  
2014 ◽  
Vol 74 (12) ◽  
pp. 1240-1248 ◽  
Author(s):  
Cheryn Song ◽  
Yunlim Kim ◽  
Gyeong Eun Min ◽  
Hanjong Ahn
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Glucocorticoid Receptor ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Osteoblasts Promote Prostate Cancer Cell Proliferation Through Androgen Receptor Independent Mechanisms

2021 ◽  
Vol 11 ◽  
Author(s):  
Giulia Ribelli ◽  
Sonia Simonetti ◽  
Michele Iuliani ◽  
Elisabetta Rossi ◽  
Bruno Vincenzi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Androgen Receptor ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Castration Resistant Prostate Cancer ◽  
Matrix Metalloproteinase 1 ◽  
Depth Analysis

Patients with metastatic prostate cancer frequently develop bone metastases that elicit significant skeletal morbidity and increased mortality. The high tropism of prostate cancer cells for bone and their tendency to induce the osteoblastic-like phenotype are a result of a complex interplay between tumor cells and osteoblasts. Although the role of osteoblasts in supporting prostate cancer cell proliferation has been reported by previous studies, their precise contribution in tumor growth remains to be fully elucidated. Here, we tried to dissect the molecular signaling underlining the interactions between castration-resistant prostate cancer (CRPC) cells and osteoblasts using in vitro co-culture models. Transcriptomic analysis showed that osteoblast-conditioned media (OCM) induced the overexpression of genes related to cell cycle in the CRPC cell line C4-2B but, surprisingly, reduced androgen receptor (AR) transcript levels. In-depth analysis of AR expression in C4-2B cells after OCM treatment showed an AR reduction at the mRNA (p = 0.0047), protein (p = 0.0247), and functional level (p = 0.0029) and, concomitantly, an increase of C4-2B cells in S-G2-M cell cycle phases (p = 0.0185). An extensive proteomic analysis revealed in OCM the presence of some molecules that reduced AR activation, and among these, Matrix metalloproteinase-1 (MMP-1) was the only one able to block AR function (0.1 ng/ml p = 0.006; 1 ng/ml p = 0.002; 10 ng/ml p = 0.0001) and, at the same time, enhance CRPC proliferation (1 ng/ml p = 0.009; 10 ng/ml p = 0.033). Although the increase of C4-2B cell growth induced by MMP-1 did not reach the proliferation levels observed after OCM treatment, the addition of Vorapaxar, an MMP-1 receptor inhibitor (Protease-activated receptor-1, PAR-1), significantly reduced C4-2B cell cycle (0.1 μM p = 0.014; 1 μM p = 0.0087). Overall, our results provide a novel AR-independent mechanism of CRPC proliferation and suggest that MMP-1/PAR-1 could be one of the potential pathways involved in this process.

scholarly journals 3-O-Carbamoyl-5,7,20-O-trimethylsilybins: Synthesis and Preliminary Antiproliferative Evaluation

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6421
Author(s):  
Sitong Wu ◽  
Guanglin Chen ◽  
Qiang Zhang ◽  
Guangdi Wang ◽  
Qiao-Hong Chen
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Water Solubility ◽  
Prostate Cancer Cell ◽  
Hydroxyl Group ◽  
Hydroxyl Groups ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Alcoholic Hydroxyl

To search for novel androgen receptor (AR) modulators for the potential treatment of castration-resistant prostate cancer (CRPC), naturally occurring silibinin was sought after as a lead compound because it possesses a moderate potency towards AR-positive prostate cancer cells and its chemical scaffold is dissimilar to all currently marketed AR antagonists. On the basis of the structure–activity relationships that we have explored, this study aims to incorporate carbamoyl groups to the alcoholic hydroxyl groups of silibinin to improve its capability in selectively suppressing AR-positive prostate cancer cell proliferation together with water solubility. To this end, a feasible approach was developed to regioselectively introduce a carbamoyl group to the secondary alcoholic hydroxyl group at C-3 without causing the undesired oxidation at C2–C3, providing an avenue for achieving 3-O-carbamoyl-5,7,20-O-trimethylsilybins. The application of the synthetic method can be extended to the synthesis of 3-O-carbamoyl-3′,4′,5,7-O-tetramethyltaxifolins. The antiproliferative potency of 5,7,20-O-trimethylsilybin and its nine 3-carbamoyl derivatives were assessed in an AR-positive LNCaP prostate cancer cell line and two AR-null prostate cancer cell lines (PC-3 and DU145). Our preliminary bioassay data imply that 5,7,20-O-trimethylsilybin and four 3-O-carbamoyl-5,7,20-O-trimethylsilybins emerge as very promising lead compounds due to the fact that they can selectively suppress AR-positive LNCaP cell proliferation. The IC50 values of these five 5,7,20-O-trimethylsilybins against the LNCaP cells fall into the range of 0.11–0.83 µM, which exhibit up to 660 times greater in vitro antiproliferative potency than silibinin. Our findings suggest that carbamoylated 5,7,20-O-trimethylsilybins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.

scholarly journals 23-O-Substituted-2,3-Dehydrosilybins Selectively Suppress Androgen Receptor-Positive LNCaP Prostate Cancer Cell Proliferation

2020 ◽  
Vol 15 (5) ◽  
pp. 1934578X2092232
Author(s):  
Ziran Jiang ◽  
Arman Sekhon ◽  
Yogeshwari Oka ◽  
Guanglin Chen ◽  
Nagat Alrubati ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Androgen Receptor ◽  
Natural Product ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cell Model ◽  
Cancer Cell Proliferation ◽  
Castration Resistant Prostate Cancer ◽  
Lncap Prostate Cancer Cell

As part of our ongoing project to search for natural product-based antiandrogens, nine derivatives of 2,3-dehydrosilybin have been synthesized for the evaluation of its antiproliferative activity in an androgen receptor-positive prostate cancer cell model. Specifically, 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin was synthesized through two approaches, and eight 23- O-substituted-3,5,7,20- O-tetramethyl-2,3-dehydrosilybins were achieved from 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin. The antiproliferative potency of 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and its eight derivatives were assessed in an androgen receptor (AR)-positive LNCaP prostate cancer cell line, as well as in two AR-negative (PC-3 and DU145) prostate cancer cell models as a comparison. Our WST cell proliferation assay data indicate 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and most of its 23- O-substituents can selectively inhibit AR-positive LNCaP prostate cancer cell proliferation. Our data suggest that 3,5,7,20- O-tetramethyl-2,3-dehydrosilibins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.

Exendin-4, a Glucagon-Like Peptide-1 Receptor Agonist, Attenuates Prostate Cancer Cell Proliferation via Phosphorylation of MKP-1

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1957-P
Author(s):  
TAKAKO KAWANAMI ◽  
TAKASHI NOMIYAMA ◽  
YURIKO HAMAGUCHI ◽  
TOMOKO TANAKA ◽  
TOSHIHIKO YANASE
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Receptor Agonist ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals SRC-3 Is Required for Prostate Cancer Cell Proliferation and Survival

2005 ◽  
Vol 65 (17) ◽  
pp. 7976-7983 ◽  
Author(s):  
Hai-Jun Zhou ◽  
Jun Yan ◽  
Weiping Luo ◽  
Gustavo Ayala ◽  
Sue-Hwa Lin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation

scholarly journals How can food extracts consumed in the Mediterranean and East Asia suppress prostate cancer proliferation?

2011 ◽  
Vol 108 (3) ◽  
pp. 424-430 ◽  
Author(s):  
Mu Yao ◽  
Chanlu Xie ◽  
Maryrose Constantine ◽  
Sheng Hua ◽  
Brett D. Hambly ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
East Asia ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Prostate Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Prostate Cancer Cells ◽  
The Mediterranean

We have developed a blend of food extracts commonly consumed in the Mediterranean and East Asia, named blueberry punch (BBP), with the ultimate aim to formulate a chemoprevention strategy to inhibit prostate cancer progression in men on active surveillance protocol. We demonstrated previously that BBP inhibited prostate cancer cell proliferation in vitro and in vivo. The purpose of this study was to determine the molecular mechanism responsible for the suppression of prostate cancer cell proliferation by BBP. Treatment of lymph node-metastasised prostate cancer cells (LNCaP) and bone-metastasised prostate cancer cells (PC-3 and MDA-PCa-2b) with BBP (up to 0·8 %) for 72 h increased the percentage of cells at the G0/G1 phase and decreased those at the S and G2/M phases. The finding was supported by the reduction in the percentage of Ki-67-positive cells and of DNA synthesis measured by the incorporation of 5-ethynyl-2′-deoxyuridine. Concomitantly, BBP treatment decreased the protein levels of phosphorylated retinoblastoma, cyclin D1 and E, cyclin-dependent kinase (CDK) 4 and 2, and pre-replication complex (CDC6 and MCM7) in LNCaP and PC-3 cells, whereas CDK inhibitor p27 was elevated in these cell lines. In conclusion, BBP exerts its anti-proliferative effect on prostate cancer cells by modulating the expression and phosphorylation of multiple regulatory proteins essential for cell proliferation.

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