The α1-adrenoceptor antagonist terazosin induces prostate cancer cell death through a p53 and Rb independent pathway

Xu, Kexin; Wang, Xianghong; Ling, Patrick; Tsao, Sai Wah; Wong, YC

doi:10.3892/or.10.5.1555

Cited by 8 publications

(6 citation statements)

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“…The cell cycle inhibitor, p27(KIP1) was also found to be activated in response to prazosin and doxazosin, a finding previously reported for several cell lines . Interestingly, AMPK activation and subsequent autophagy may also be associated with significant increases in p27 expression and the AMPK pathway has been reported to regulate p27‐mediated inhibition of cell cycle progression and autophagy .…”

Section: Discussionsupporting

confidence: 56%

Relative cytotoxic potencies and cell death mechanisms of α₁‐adrenoceptor antagonists in prostate cancer cell lines

et al. 2016

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Section: Discussionsupporting

confidence: 56%

Relative cytotoxic potencies and cell death mechanisms of α₁‐adrenoceptor antagonists in prostate cancer cell lines

et al. 2016

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“…The mechanisms of apoptosis induction seem to be α 1A -AR independent. , Putative mechanisms underlying doxazosin-mediated apoptosis include the up-regulation of transforming growth factor beta (TGF-beta) signaling effectors , and blocking of intracellular protein kinase B/Akt activation . Terazosin-induced PC-3 and DU-145 cancer cells death is p53- and Rb-independent and is associated with G1 phase cell cycle arrest, up-regulation of p27Kip1 and Bax, and down-regulation of bcl-2, − and I kappa B alpha induction …”

Section: Introductionmentioning

confidence: 99%

Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 8. {2-[2-(4-Chlorobenzyloxy)phenoxy]ethyl}-[2-(2,6-dimethoxyphenoxy)ethyl]amine (Clopenphendioxan) as a Tool to Highlight the Involvement of α_1D- and α_1B-Adrenoreceptor Subtypes in the Regulation of Human PC-3 Prostate Cancer Cell Apoptosis and Proliferation

et al. 2005

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A series of new alpha1-adrenoreceptor antagonists (5-18) was prepared by introducing various substituents (Topliss approach) into the ortho, meta, and para positions of the benzyloxy function of the phendioxan open analogue 4 ("openphendioxan"). All the compounds synthesized were potent antagonists and generally displayed, similarly to 4, the highest affinity values at alpha1D- with respect to alpha1A- and alpha1B-AR subtypes and 5-HT1A subtype. By sulforhodamine B (SRB) assay on human PC-3 prostate cancer cells, the new compounds showed antitumor activity (estimated on the basis of three parameters GI50, TGI, LC50), at low micromolar concentration, with 7 ("clopenphendioxan") exhibiting the highest efficacy. Moreover, this study highlighted for the first time alpha1D- and alpha1B-AR expression in PC3 cells and also demonstrated the involvement of these subtypes in the modulation of apoptosis and cell proliferation. A significant reduction of alpha1D- and alpha1B-AR expression in PC3 cells was associated with the apoptosis induced by 7. This depletion was completely reversed by norepinephrine.

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“…This study is the first to reveal its potential as a UXT-AS1 targeting drug in cancers. For another drug, terazosin, previous studies have shown an anti-cancer effect in urinary tract tumors, especially in prostate cancer [80][81][82][83][84][85][86]. Previous studies have shown that terazosin inhibits tumors in prostate cancer by inducing apoptosis [81,84,85], this mechanism may be played through a p53 and Rb independent pathway [82].…”

Section: Discussionmentioning

confidence: 99%

UXT antisense RNA 1 sever as a novel prognostic long non-coding RNA in early stage pancreatic ductal adenocarcinoma patients after receiving pancreaticoduodenectomy

Liao¹,

Huang²,

Wang³

et al. 2021

J. Cancer

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Objective: The principal objective of this project was to investigate the prognostic value of UXT antisense RNA 1 (UXT-AS1) in pancreatic ductal adenocarcinoma (PDAC), as well as its biological function mechanisms and the screening of targeted drugs using The Cancer Genome Atlas (TCGA) PDAC genome-wide RNA sequencing (RNA-seq) dataset. Methods: We used TCGA 112 early stage PDAC patients to screen the prognostic value of UXT-AS1. Biological functions and mechanisms of UXT-AS1 were investigated by co-expression analysis, differentially expressed genes (DEGs) and gene set enrichment analysis, while targeted drug screening was investigated by connectivity Map (CMap). Results: By analyzing the dataset from TCGA cohort, we found that UXT-AS1 was significantly up-regulated in pancreatic cancer tissues. Multivariate survival analysis demonstrated that PDAC patients with high UXT-AS1 expression had an unfavourable prognosis (adjusted P=0.033, HR=1.830, 95%CI=1.051-3.188). Genome-wide co-expression analysis and gene set enrichment analysis suggested that UXT-AS1 may act as a pivotal part in PDAC by participating in nuclear factor kappa beta, regulation of tumor necrosis factor, cell adhesion, T cell receptor signaling pathway, and numerous immune-related biological processes and signaling pathways. Functional enrichment analysis of DEGs between high-and low-UXT-AS1 expression groups suggested that these DEGs were significant enriched in B cell receptor complex, response to drug chemical carcinogenesis and drug metabolism-cytochrome P450. CMap analysis revealed that quipazine and terazosin may be targeted drugs for UXT-AS1 in PDAC. Conclusion: Our current study has identified UXT-AS1 as a novel biomarker for the prognosis of early stage PDAC. We also clarified its biological functional mechanisms and identified two targeted drugs of UXT-AS1 in PDAC.

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The α1-adrenoceptor antagonist terazosin induces prostate cancer cell death through a p53 and Rb independent pathway

Cited by 8 publications

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Relative cytotoxic potencies and cell death mechanisms of α₁‐adrenoceptor antagonists in prostate cancer cell lines

Relative cytotoxic potencies and cell death mechanisms of α₁‐adrenoceptor antagonists in prostate cancer cell lines

UXT antisense RNA 1 sever as a novel prognostic long non-coding RNA in early stage pancreatic ductal adenocarcinoma patients after receiving pancreaticoduodenectomy

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The α1-adrenoceptor antagonist terazosin induces prostate cancer cell death through a p53 and Rb independent pathway

Cited by 8 publications

References 0 publications

Relative cytotoxic potencies and cell death mechanisms of α1‐adrenoceptor antagonists in prostate cancer cell lines

Relative cytotoxic potencies and cell death mechanisms of α1‐adrenoceptor antagonists in prostate cancer cell lines

UXT antisense RNA 1 sever as a novel prognostic long non-coding RNA in early stage pancreatic ductal adenocarcinoma patients after receiving pancreaticoduodenectomy

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Relative cytotoxic potencies and cell death mechanisms of α₁‐adrenoceptor antagonists in prostate cancer cell lines

Relative cytotoxic potencies and cell death mechanisms of α₁‐adrenoceptor antagonists in prostate cancer cell lines