Background: Prostate cancer is the second leading cause of cancer-related death among males in America. The patients' survival time is significantly reduced after prostate cancer develops into castration-resistant prostate cancer (CRPC). It has been reported that AKR1C3 is involved in this progression, and that its abnormal expression is directly correlated with the degree of CRPC malignancy. Genistein is one of the active components of soy isoflavones, and many studies have suggested that it has a better inhibitory effect on CRPC.
Objective: This study aimed to investigate the antitumor effect of genistein on CRPC and the potential mechanism of action.
Design: A xenograft tumor mouse model established with 22RV1 cells was divided into the experimental group and the control group, and the former was given 100 mg/kg.bw/day of genistein, with 22RV1, VCaP, and RWPE-1 cells cultured in a hormone-free serum environment and treated with different concentrations of genistein (0, 12.5, 25, 50, and 100 μmol/L) for 48 h. Molecular docking was used to elucidate the molecular interactions between genistein and AKR1C3.
Results: Genistein inhibits CRPC cell proliferation and in vivo tumorigenesis. The western blot analysis confirmed that the genistein significantly inhibited prostate-specific antigen production in a dose-dependent manner. In further results, AKR1C3 expression was decreased in both the xenograft tumor tissues and the CRPC cell lines following genistein gavage feeding compared to the control group, with the reduction becoming more obvious as the concentration of genistein was increased. When the genistein was combined with AKR1C3 small interfering ribonucleic acid and an AKR1C3 inhibitor (ASP-9521), the inhibitory effect on the AKR1C3 was more pronounced. In addition, the molecular docking results suggested that the genistein had a strong affinity with the AKR1C3, and that it could be a promising AKR1C3 inhibitor.
Conclusion: Genistein inhibits the progression of CRPC via the suppression of AKR1C3.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9899042 | PMC |
| http://dx.doi.org/10.29219/fnr.v67.9024 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.
J Clin Oncol
January 2025
Jefferson Einstein Medical Center, Sidney Kimmel Cancer Center of Thomas Jefferson University, Philadelphia, PA.
Purpose: To evaluate evidence on germline and somatic genomic testing for patients with metastatic prostate cancer and provide recommendations.
Methods: A systematic review by a multidisciplinary panel with patient representation was conducted. The PubMed database was searched from January 2018 to May 2024.
Adult Embryonal Rhabdomyosarcoma of the Prostate Presented on 18F-FDG and Al18F-FAPI-74 PET/CT.
Clin Nucl Med
December 2024
From the Department of Nuclear Medicine (PET-CT Center), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
A 21-year-old man with a 2-week history of abdominal pain and urinary hesitancy was admitted to our hospital. Sarcoma was suspected based on his PSA level, age, and MRI findings. He underwent 18F-FDG and Al18F-FAPI-74 PET/CT scans.
View Article and Find Full Text PDFNXP800 activates the unfolded protein response, altering AR and E2F function to impact castration-resistant prostate cancer growth.
Clin Cancer Res
January 2025
Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Purpose: Advanced prostate cancer (PCa) is invariably fatal with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced PCa, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need.
View Article and Find Full Text PDFExploring the link between sex hormone-binding globulin levels and prostate cancer risk: a comprehensive systematic review and meta-analysis.
Int Urol Nephrol
January 2025
Faculty of Data Science and Information Technology, INTI International University, Nilai, Malaysia.
Background: Sex hormone-binding globulin (SHBG) plays a critical role in regulating androgen bioavailability and has been hypothesized to influence prostate cancer risk, though existing evidence is inconsistent. This systematic review and meta-analysis aimed to evaluate the association between SHBG levels and prostate cancer risk.
Methods: A comprehensive search was conducted across PubMed, Embase, and Web of Science for studies published up to December 1, 2024.
Evaluating the prognostic value of radiomics and clinical features in metastatic prostate cancer using [Ga]Ga-PSMA-11 PET/CT.
Phys Eng Sci Med
January 2025
School of Physics, Mathematics and Computing, University of Western Australia, Crawley, WA, Australia.
Prostate cancer is a significant global health issue due to its high incidence and poor outcomes in metastatic disease. This study aims to develop models predicting overall survival for patients with metastatic biochemically recurrent prostate cancer, potentially helping to identify high-risk patients and enabling more tailored treatment options. A multi-centre cohort of 180 such patients underwent [Ga]Ga-PSMA-11 PET/CT scans, with lesions semi-automatically segmented and radiomic features extracted from lesions.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!