bims-meproc 2025-04-20 papers

Issue of 2025–04–20
three papers selected by
Grigor Varuzhanyan, UCLA

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 14.

Effects of empagliflozin and its combination with docetaxel on LNCaP and DU- 145 prostate cancer cell lines: cytotoxicity and molecular pathway analysis.

Ahmet Cumaoğlu, Selda Nur Akdeniz, Ahmad Karzoon, Mohamed Alaama, Mükerrem Betül Yerer.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have gained attention for their potential therapeutic applications in cancer treatment. Recent Mendelian randomization and observational analyses support the protective role of SGLT2 inhibition in reducing prostate cancer risk. Additionally, SGLT2 expression in prostate cancer patient samples has been confirmed through immunohistochemistry. The therapeutic potential of empagliflozin, a selective SGLT2 inhibitor, in treating prostate cancer, either alone or with chemotherapeutic agents like docetaxel, remains largely unexplored. This study investigated the cytotoxic and synergistic effects of empagliflozin in combination with docetaxel in LNCaP and DU- 145 prostate cancer cells. Cell viability was assessed using the MTT assay, and synergy was evaluated using the Chou-Talalay method. Western blot analysis was conducted to examine the effects of empagliflozin, alone and in combination with docetaxel, on key molecular targets, including p-AMPKα, p-p70S6 K1, p-PRAS40, and p-Akt. Empagliflozin exhibited concentration-dependent cytotoxic effects in both LNCaP and DU- 145 cells, with a higher potency observed in DU- 145 cells. When combined with docetaxel, empagliflozin demonstrated synergistic activity, as indicated by combination index values < 1. Empagliflozin upregulated p-AMPKα and downregulated p-p70S6 K1 and p-PRAS40. The combination with docetaxel further enhanced these effects. Notably, empagliflozin alone downregulated p-Akt in LNCaP cells but not in DU- 145 cells, highlighting cell-line-specific differences. Empagliflozin reduces prostate cancer cell viability and enhances the cytotoxic effects of docetaxel, suggesting a promising combination strategy for prostate cancer therapy. Additional in vivo studies and clinical trials are needed to assess the translational relevance of these findings.

Keywords: AMPKα; Empagliflozin; P70S6 K1; PGC- 1α; PRAS40; Prostate cancer

DOI: https://doi.org/10.1007/s00210-025-04132-9

Comput Biol Chem. 2025 Apr 10. pii: S1476-9271(25)00119-7. [Epub ahead of print]118 108459

Transcriptomic analysis of human castration-resistant prostate cancer: Insights into novel therapeutic strategies.

Ramanjaneyulu Golla, Sneha Jaiswal, Anaswara Jayan, Srinivasulu Cheemanapalli.

Prostate cancer is a major cause of cancer-related deaths in men worldwide. Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer; however, disease progression to castration-resistant prostate cancer (CRPC) presents a significant therapeutic challenge. In this study, we employed transcriptomic analysis to investigate key genetic drivers of CRPC and identify novel therapeutic targets. Using RNA-seq data and bioinformatics tools, we identified differentially expressed genes (DEGs) associated with tumor progression, cytoskeletal dynamics, and immune modulation, including COL3A1, MYH4, FN1, ACTN1, and CALR. Functional enrichment analysis revealed significant involvement of actin-myosin filament sliding, calcium signaling, androgen receptor signaling, immune evasion, and metabolic pathways, underscoring their roles in CRPC progression and treatment resistance. Additionally, molecular docking studies demonstrated strong binding interactions between key CRPC-related genes (ABCC4 and FOLH1) and potential therapeutic ligands, including flutamide and N-acetyl glucosamine (NAG), highlighting their therapeutic potential in overcoming drug resistance. These findings provide novel insights into the molecular landscape of CRPC and support the development of precision-targeted therapies to improve patient outcomes.

Keywords: Androgen deprivation therapy (ADT); Bioinformatics; Castration-resistant prostate cancer (CRPC); Immunotherapy; Multivalent peptoid conjugates (MPC); Next-generation sequencing; Personalized medicine; Prostate Cancer

DOI: https://doi.org/10.1016/j.compbiolchem.2025.108459

Transl Androl Urol. 2025 Mar 30. 14(3): 553-566

From obesity to inflammation: emerging frontiers in prostate cancer and metabolic syndrome studies.

Xi Xu, Jinshan Xu, Hongliang Gao, Zhaoyang Sheng, Yang Xu, Shuxiong Zeng, Guanghua Chen, Zhensheng Zhang.

Background: According to recent studies, prostate cancer (PCa) is strongly associated with metabolic syndrome (MetS). However, there has not been any bibliometric visual analysis of relevant papers. In order to acquire knowledge about research settings and possible future paths, a thorough bibliometric study of MetS-related PCa research was carried out.
Methods: From January 1, 2004 to December 31, 2023, original and review publications about MetS and PCa were retrieved from the Web of Science Core Collection (WOSCC) database. Analysis of co-authorship and co-occurrence was done using VOSviewer. To find the top terms with the greatest citation burst, CiteSpace was used.
Results: There were 1,296 publications on PCa and MetS in all. The analysis showed that the number of yearly scientific papers in the sector was on the rise. The three most productive nations were China, Italy, and the USA. Most papers were published in the PLoS One, while most citations were obtained by the European Urology. The most influential author in terms of citations was Professor Smith MR, whereas the most prolific author was Professor Freedland SJ. Keyword analysis revealed that, apart from PCa and MetS, "obesity" was the most often used phrase, with "risk", "meta-analysis", and "inflammation" appearing as study subjects. Furthermore, "components" and "sex hormones" gained more and more attention.
Conclusions: The findings provide a thorough understanding of the larger context of this field of study. Future studies need to investigate PCa's metabolic processes and inflammatory mechanism. Furthermore, switching from observational research to meta-analysis offers the possibility of illness prediction and tailored therapies. These results may help researchers navigate the most recent advancements and influence the field's future paths.

Keywords: Prostate cancer (PCa); bibliometric; inflammation; metabolic syndrome (MetS); obesity

DOI: https://doi.org/10.21037/tau-2024-671