The antiandrogenic effect of finasteride against a mutant androgen receptor

Wu, Yue; Chhipa, Rishi Raj; Zhang, Haitao; Ip, Clement

doi:10.4161/cbt.11.10.15187

Cited by 21 publications

(17 citation statements)

References 24 publications

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“…In our previous study, 10 nM insulin increased intracellular testosterone levels 60-fold in LNCaPs; here, IGF2 increased testosterone The varying amounts of steroidogenesis occurring in our cell lines, in absolute levels, as well as induction, may partially reflect their relative AR mutation status. LNCaP, VCaP and 22RV1 are androgen responsive; however, each cell line expresses different forms of AR; LNCaP AR harbours the T877A mutation, which renders it promiscuous (Veldscholte et al 1990), and 22RV1 cells express the less promiscuous AR mutation, H874Y, along with a truncated, constitutively active AR (Tepper et al 2002), whereas VCaPs express wild-type AR (Wu et al 2011). Interestingly, 22RV1s, which have the most cumulative AR mutations, appear to be most steroidogenic in regard to absolute levels of DHT and testosterone synthesis; furthermore, LNCaP cells produce more de novo testosterone and DHT than VCaP cells, which are documented to have the least AR mutations.…”

Section: Discussionmentioning

confidence: 99%

IGF2 increases de novo steroidogenesis in prostate cancer cells

Lubik¹,

Gunter²,

Hollier³

et al. 2013

Endocrine-Related Cancer

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IGF2 is a mitogenic foetal growth factor commonly over-expressed in cancers, including prostate cancer (PC). We recently demonstrated that insulin can activate de novo steroidogenesis in PC cells, a major pathway for reactivation of androgen pathways and PC progression. IGF2 can activate the IGF1 receptor (IGF1R) or insulin receptor (INSR) or hybrids of these two receptors. We therefore hypothesized that IGF2 may contribute to PC progression via de novo steroidogenesis. IGF2 mRNA but not IGF2 receptor mRNA expression was increased in patient samples during progression to castrate-resistant PC as was immunoreactivity to INSR and IGF1R antibodies. Treatment of androgen receptor (AR)-positive PC cell lines LNCaP and 22RV1 with IGF2 for 48 h resulted in increased expression of steroidogenic enzyme mRNA and protein, including steroid acute regulatory protein (StAR), cytochrome p450 family member (CYP)17A1, aldo-keto reductase family member (AKR)1C3 and hydroxysteroid dehydrogenase (HSD)17B3. IGF2 treatment resulted in increased steady state steroid levels and increased de novo steroidogenesis resulting in AR activation as demonstrated by PSA mRNA induction. Inhibition of the IGF1R/INSR signalling axis attenuated the effects of IGF2 on steroid hormone synthesis. We present a potential mechanism for prostatic IGF2 contributing to PC progression by inducing steroidogenesis and that IGF2 signalling and related pathways present attractive targets for PC therapy.

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Section: Discussionmentioning

confidence: 99%

IGF2 increases de novo steroidogenesis in prostate cancer cells

Lubik¹,

Gunter²,

Hollier³

et al. 2013

Endocrine-Related Cancer

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“…However, prolonged adverse effects on sexual function such as erectile dysfunction, diminished libido, depression, and decreased quality of life, are reported by a subset of men [109]. As the described symptoms seem to apply to 5ARis in general and manifest mainly after 5ARi withdrawal, this condition has been identified as a new medical problem, 5ARi Withdrawal Syndrome [110].…”

Section: A-reductase Inhibitors (5ari)mentioning

confidence: 99%

Androgenetic alopecia: a review

et al. 2017

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Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms at different genomic loci are associated with androgenetic alopecia development. A number of genes determine the predisposition for androgenetic alopecia in a polygenic fashion. However, further studies are needed before the specific genetic factors of this polygenic condition can be fully explained.

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“…PRDX1 enhances AR function in prostate cancer cells through increasing affinity of AR to dihydrotestosterone (DHT) [31]. In PRDX1-rich LNCap cells, the combination of PRDX1 knockdown and finasteride, a structural analogue of DHT, was found to produce a greater inhibitory effect on AR activity and cell growth than either treatment alone [108]. The above findings suggest that PRDX1 may play a critical role in the context of developing strategies to improve the outcome of androgen deprivation therapy in prostate cancer.…”

Section: Prdx1 and Prostate Cancermentioning

confidence: 99%

Peroxiredoxin 1 – an antioxidant enzyme in cancer

Ding

Fan

2016

J Cellular Molecular Medi

171

131

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Peroxiredoxins (PRDXs), a ubiquitous family of redox‐regulating proteins, are reported of potential to eliminate various reactive oxygen species (ROS). As a major member of the antioxidant enzymes, PRDX1 can become easily over‐oxidized on its catalytically active cysteine induced by a variety of stimuli in vitro and in vivo. In nucleus, oligomeric PRDX1 directly associates with p53 or transcription factors such as c‐Myc, NF‐κB and AR, and thus affects their bioactivities upon gene regulation, which in turn induces or suppresses cell death. Additionally, PRDX1 in cytoplasm has anti‐apoptotic potential through direct or indirect interactions with several ROS‐dependent (redox regulation) effectors, including ASK1, p66Shc, GSTpi/JNK and c‐Abl kinase. PRDX1 is proven to be a versatile molecule regulating cell growth, differentiation and apoptosis. Recent studies have found that PRDX1 and/or PRDX1‐regulated ROS‐dependent signalling pathways play an important role in the progression and metastasis of human tumours, particularly in breast, oesophageal and lung cancers. In this paper, we review the structure, effector functions of PRDX1, its role in cancer and the pivotal role of ROS in anticancer treatment.

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The antiandrogenic effect of finasteride against a mutant androgen receptor

Cited by 21 publications

References 24 publications

IGF2 increases de novo steroidogenesis in prostate cancer cells

IGF2 increases de novo steroidogenesis in prostate cancer cells

Androgenetic alopecia: a review

Peroxiredoxin 1 – an antioxidant enzyme in cancer

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