Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor

Cheng, Chen-Li; Gao, Guanlun; Ho, Dong-Ru; Lin, Chih-Yi; Chou, Yu-Ting; Chen, Shanchun; Huang, Mincong; Kao, Wen-Ya; Su, Jyan-Gwo J.

doi:10.1038/s41598-021-84769-7

Cited by 7 publications

(2 citation statements)

References 46 publications

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“…However, the related results are controversial. In vitro studies have shown that the antiandrogens cyproterone acetate and flutamide have inhibitory effects on androgen-induced HCC cell growth ( Koch et al, 2015 ; Chen et al, 2021 ). In contrast, large clinical trials with leuprolide and flutamide (antiandrogens) have failed to improve patient survival ( GdEedTdC, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Integrative pan-cancer landscape of MMS22L and its potential role in hepatocellular carcinoma

2022

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Methyl methanesulfonate-sensitivity protein 22-like (MMS22L) is crucial in protecting genome integrity during DNA replication by preventing DNA damage and maintaining efficient homologous recombination. However, the role of MMS22L in human cancers remains unclear. Here, we reported the landscape of MMS22L using multi-omics data and identified the relationship between the MMS22L status and pan-cancer prognosis. In addition, the correlation of MMS22L mRNA expression levels with tumor mutational burden, microsatellite instability, homologous recombination deficiency, and loss of heterozygosity in pan-cancer was also described in this study. Furthermore, this study was the first to characterize the relationship between mRNA expression of MMS22L and immune cell infiltration in the tumor microenvironment in human cancer. Concurrently, this study explored the crucial role of MMS22L in different immunotherapy cohorts through current immunotherapy experiments. Eventually, we investigated the role of MMS22L in hepatocellular carcinoma (HCC). The results demonstrated that MMS22L is widely expressed in multiple HCC cell lines, and our results emphasized that MMS22L was involved in HCC progression and affects the prognosis of patients with HCC through multiple independent validation cohorts. Collectively, our findings reveal the essential role of MMS22L as a tumor-regulating gene in human cancers while further emphasizing its feasibility as a novel molecular marker in HCC. These findings provide an essential reference for the study of MMS22L in tumors.

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Section: Discussionmentioning

confidence: 99%

Integrative pan-cancer landscape of MMS22L and its potential role in hepatocellular carcinoma

2022

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“…Ethynyl estradiol (a synthetic estrogen used as contraceptive drug) caused liver effects (congestion, focal areas of hemorrhage, vacuolation of cytoplasm, distended sinusoids with dilated central veins) in female rats and the extent and severity of the damage depends on the dose and the time of administration [23]. More recently, CPA demonstrated also to be an aryl hydrocarbon receptor (AhR) agonist in mouse and an AhR antagonist in human cells [24]. Indeed, in both male and female C57BL/10J mice, long-term exposure to 800 ppm of CPA in the diet induced hepatocyte hypertrophy and increased fat and glycogen [25].…”

Section: Discussionmentioning

confidence: 99%

Risk Assessment of Transgender People: Development of Rodent Models Mimicking Gender-Affirming Hormone Therapies and Identification of Sex-Dimorphic Liver Genes as Novel Biomarkers of Sex Transition

Tassinari¹,

Tammaro²,

Lori³

et al. 2022

Preprint

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Transgender (TG) describes individuals whose gender identity differs from the social norms. Some TG people undergo gender-affirming hormone therapy (HT) and may be considered as a sub-group of population susceptible to environmental contaminants for their targets and modes of action. Aim of the work is to set appropriate HT doses and identify specific biomarkers to implement TG animal models. Four adult rats/group/sex are subcutaneously exposed to 3 doses of HT (plus control) selected starting from available data. Demasculinizing-feminizing model (dMF): β-estradiol plus cyproterone acetate: 0.09+0.33, 0.09+0.93 and 0.18+0.33 mg, 5 times/week. Defeminizing-masculinizing model (dFM): testosterone 0.45, 0.95 and 2.05 mg, 2 times/week. Clitoral gain and sperm count, histophatological analysis of reproductive organs and liver, hormone serum levels and gene expression of sex-dimorphic CYP450 are evaluated. In dMF model, the selected doses, leading to T serum levels at the range of the corresponding cisgender, induced strong general toxicity and cannot be used in long-term studies. In dFM model, 0.45 mg of testosterone represents the correct dose. In addition, the endpoints selected are considered suitable and reliable to implement the animal model. The sex-specific CYP expression is a suita-ble biomarker to set proper (de)masculinizing/(de)feminizing HT and to implement TG animal models.

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PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade

Guo,

Zhang,

Shen

et al. 2024

Cell Biol Toxicol

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Programmed cell death ligand 2 (PD-L2), a ligand for the receptor programmed cell death 1 (PD-1), has an identity of 34% with its twin ligand PD-L1 and exhibits higher binding affinity with PD-1 than PD-L1. However, the role of PD-L2 in non-small cell lung cancer (NSCLC) progression, especially tobacco-induced cancer progression, has not been fully understood. Here, we found that PD-L2 promoted tumor growth in murine models with recruitment of regulatory T cells (Tregs). In patients with NSCLC, PD-L2 expression level in tumor samples was higher than in counterpart normal controls and was positively associated with patients’ response to anti-PD-1 treatment. Mechanismly, PD-L2 bound its receptor Repulsive guidance molecule B (RGMB) on cancer cells and activated extracellular signal-regulated kinase (Erk) and nuclear factor κB (NFκB), leading to increased production of chemokine CCL20, which recruited Tregs and contributed to NSCLC progression. Consistently, knockdown of RGMB or NFκB p65 inhibited PD-L2-induced CCL20 production, and silencing of PD-L2 repressed Treg recruitment by NSCLC cells. Furthermore, cigarette smoke and carcinogen benzo(a)pyrene (BaP) upregulated PD-L2 in lung epithelial cells via aryl hydrocarbon receptor (AhR)-mediated transcription activation, whose deficiency markedly suppressed BaP-induced PD-L2 upregulation. These results suggest that PD-L2 mediates tobacco-induced recruitment of Tregs via the RGMB/NFκB/CCL20 cascade, and targeting this pathway might have therapeutic potentials in NSCLC.

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Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor

Cited by 7 publications

References 46 publications

Integrative pan-cancer landscape of MMS22L and its potential role in hepatocellular carcinoma

Integrative pan-cancer landscape of MMS22L and its potential role in hepatocellular carcinoma

Risk Assessment of Transgender People: Development of Rodent Models Mimicking Gender-Affirming Hormone Therapies and Identification of Sex-Dimorphic Liver Genes as Novel Biomarkers of Sex Transition

PD-L2 mediates tobacco smoking-induced recruitment of regulatory T cells via the RGMB/NFκB/CCL20 cascade

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