Inhibiting 3βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer

Hou, Zhufeng; Huang, Shengsong; Mei, Zejie; Chen, Longlong; Guo, Jiacheng; Gao, Yuanyuan; Zhuang, Qian; Zhang, Xuebin; Tan, Qilong; Yang, Tao; Liu, Ying; Chi, Yongnan; Qi, Li-Feng-Rong; Jiang, Ting; Shao, Xuefeng; Wu, Yunpeng; Xu, Xiaojun; Qin, Jun; Ren, Ruobing; Tang, Huiru; Wu, Denglong; Li, Zhenfei

doi:10.1016/j.xcrm.2022.100561

Cited by 16 publications

(29 citation statements)

References 75 publications

(107 reference statements)

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“…Recently, we revealed that corylin and its derivatives, including biochanin A (BCA) and daidzein, bound to and inhibited 3βHSD1 ( Figure 4 A). 35 , 36 BCA, as the most potent 3βHSD1 inhibitor discovered so far, inhibited the conversion of DHEA to AD in a dose-dependent fashion ( Figure 4 B). Furthermore, BCA suppressed the function of the 3βHSD1 (367T) and 3βHSD1 (367N) isoforms comparably ( Figure 4 C).…”

Section: Resultsmentioning

confidence: 93%

Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment

Mei

Yang

Liu

et al. 2022

Cell Reports Medicine

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Section: Resultsmentioning

confidence: 93%

Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment

Mei

Yang

Liu

et al. 2022

Cell Reports Medicine

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“…Biomarkers predicting abiraterone responses will benefit patient stratification and may provide potential targets for further disease management. [6][7][8] Biomarkers from liquid biopsies have recently attracted more attention and have been widely used in clinical practice. 9 Circulating androgen receptor splice variant-7 (AR-v7) has been confirmed as a risk factor for poor clinical response in patients receiving abiraterone treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Serum sex steroids such as estradiol (E), DHEA, and progesterone have been identified as prognostic biomarkers in patients receiving ADT. 6,12 Among patients with metastatic prostate cancer treated with ADT, those with high baseline serum prolactin had worse survival compared to those with low baseline serum prolactin. 13 However, the correlation between serum hormones and abiraterone response has rarely been evaluated.…”

Section: Introductionmentioning

confidence: 99%

“…However, not all patients respond well to abiraterone therapy, and drug resistance is inevitable. Biomarkers predicting abiraterone responses will benefit patient stratification and may provide potential targets for further disease management 6–8 …”

Section: Introductionmentioning

confidence: 99%

“…Serum hormones, with well‐established detection methods, may be potential ideal biomarkers. Serum sex steroids such as estradiol (E), DHEA, and progesterone have been identified as prognostic biomarkers in patients receiving ADT 6,12 . Among patients with metastatic prostate cancer treated with ADT, those with high baseline serum prolactin had worse survival compared to those with low baseline serum prolactin 13 .…”

Section: Introductionmentioning

confidence: 99%

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Serum prolactin level as a predictive factor for abiraterone response in patients with metastatic castration‐resistant prostate cancer

et al. 2022

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Background To investigate the prognostic value and potential therapeutic target of the baseline serum hormones in patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with abiraterone. Methods This retrospective study was performed in patients with mCRPC receiving abiraterone acetate (AA) from July 2016 to September 2020. Patients who had serum hormone tests within 2 weeks before AA treatment were included. Univariate analysis and Cox regression were performed to evaluate the correlation of sex hormones with progression‐free survival (PFS) and overall survival (OS). Prolactin (PRL) expression in the clinical specimens was evaluated by immunohistochemistry. Bone metastases were quantified by automated Bone Scan Index (aBSI). Results The study included 61 patients with a median follow‐up of 19.0 months. Patients with lower baseline PRL levels (median) responded better to AA than those with higher baseline PRL levels as indicated by prostate‐specific antigen (PSA) reduction (PSA90, 66.7% vs. 25.8%, p = 0.001), PFS (19.6 vs. 7.9 months), and OS (52.8 vs. 19.2 months). Cox regression adjusted for clinical factors also confirmed that baseline PRL level was an independent predictive factor for PFS (hazard ratio = 1.096, p = 0.007). Prostatic PRL expression increased as the disease progressed. PRL expression was also detected in biopsy samples from bone metastasis but not in normal bone tissue, and the serum PRL levels were positively correlated with aBSIs (r = 0.28, p = 0.037). Conclusions Serum PRL levels are predictive of response to AA in patients with mCRPC. Serum PRL levels are positively correlated with the volume of metastatic bone disease.

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The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus

Zhang

Ding

et al. 2023

Advanced Science

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Systemic lupus erythematosus (SLE) is a complex autoimmune disease with abnormal activation of the immune system. Recent attention is increasing about how aberrant lipid and cholesterol metabolism is linked together with type I interferon (IFN‐I) signaling in the regulation of the pathogenesis of SLE. Here, a metabonomic analysis is performed and increased plasma concentrations of oxysterols, especially 7α, 25‐dihydroxycholesterol (7α, 25‐OHC), are identified in SLE patients. The authors find that 7α, 25‐OHC binding to its receptor Epstein–Barr virus‐induced gene 2 (EBI2) in macrophages can suppress STAT activation and the production of IFN‐β, chemokines, and cytokines. Importantly, monocytes/macrophages from SLE patients and mice show significantly reduced EBI2 expression, which can be triggered by IFN‐γ produced in activated T cells. Previous findings suggest that EBI2 enhances immune cell migration. Opposite to this effect, the authors demonstrate that EBI2‐deficient macrophages produce higher levels of chemokines and cytokines, which recruits and activates myeloid cells,T and B lymphocytes to exacerbate tetramethylpentadecane‐induced SLE. Together, via sensing the oxysterol 7α, 25‐OHC, EBI2 in macrophages can modulate innate and adaptive immune responses, which may be used as a potential diagnostic marker and therapeutic target for SLE.

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Inhibiting 3βHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer

Cited by 16 publications

References 75 publications

Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment

Management of prostate cancer by targeting 3βHSD1 after enzalutamide and abiraterone treatment

Serum prolactin level as a predictive factor for abiraterone response in patients with metastatic castration‐resistant prostate cancer

The Oxysterol Receptor EBI2 Links Innate and Adaptive Immunity to Limit IFN Response and Systemic Lupus Erythematosus

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