bims-meproc Biomed News
on Metabolism in Prostate Cancer
Issue of 2025–03–30
seventeen papers selected by
Grigor Varuzhanyan, UCLA
  1. Gut microbiota-derived metabolite phenylacetylglutamine inhibits the progression of prostate cancer by suppressing the Wnt/β-catenin signaling pathway.
  2. Lipid-metabolism-focused CRISPR screens identify enzymes of the mevalonate pathway as essential for prostate cancer growth.
  3. Silencing of PODXL2 Modulates Cell Viability and Tumor Immune Microenvironment of Prostate Cancer and Involves PI3K/AKT Pathway Inactivation.
  4. The combination of poly(ADP-ribose) polymerase inhibitor and statin inhibits the proliferation of human castration-resistant and taxane-resistant prostate cancer cells in vitro and in vivo.
  5. Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition.
  6. Inhibition of Steroidogenesis in Prostate Cancer Cells by Both a Natural and Another Synthetic Steroid.
  7. Lanatoside C Inhibits Proliferation and Induces Apoptosis in Human Prostate Cancer Cells Through the TNF/IL-17 Signaling Pathway.
  8. The MicroRNA miR-454 and the mediator complex component MED12 are regulators of the androgen receptor pathway in prostate cancer.
  9. Characterization of lncRNA-protein interactions associated with Prostate cancer and Androgen receptors by molecular docking simulations.
  10. Dual-tracer PET/CT for lung and prostate cancer: 18F-FDG and 18F-PSMA-1007.
  11. Contemporary real-world treatment in metastatic hormone-sensitive prostate cancer: US, four European countries, and UK.
  12. Gut microbiome, dietary habits, and prostate cancer: a two-step Mendelian randomization revealing the causal associations.
  13. Low dose Taxol causes mitochondrial dysfunction in actively respiring cancer cells.
  14. Uncovering New Biomarkers for Prostate Cancer Through Proteomic and Network Analysis.
  15. Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-β1 signaling mechanism.
  16. A novel equation synthesis for estimating resting energy expenditure in prostate cancer patients.
  17. Zoledronic acid in metastatic castrate-sensitive prostate cancer: A state-of-the-art review.
  1. Front Pharmacol. 2025 ;16 1528058
    Gut microbiota-derived metabolite phenylacetylglutamine inhibits the progression of prostate cancer by suppressing the Wnt/β-catenin signaling pathway.
    Jing Lv, Shengkai Jin, Yuhua Zhou, Chaowei Fu, Yang Shen, Bo Liu, Jufa Li, Menglu Li, Yuwei Zhang, Ninghan Feng.
       Background: Prostate cancer is one of the most common malignant tumors among men worldwide, and current treatments still face many challenges. Therefore, researchers are continuously seeking new therapeutic methods to improve treatment efficacy and reduce side effects. Phenylacetylglutamine (PAGln), a common metabolite of the gut microbiota, has been reported to have anti-inflammatory and anti-tumor activities.
    Methods: We assessed the impact of PAGln on prostate cancer using in vitro and in vivo models. Cell proliferation, migration, and invasion capabilities were evaluated through CCK8, EdU incorporation, and colony formation assays, as well as wound healing and Transwell assays. The in vivo anti-cancer effects of PAGln were evaluated using a BALB/c nude mouse xenograft model of prostate cancer and a lung metastatic tumor model established via tail vein injection. Molecular mechanisms were investigated through qRT-PCR and Western blot analysis.
    Results: PAGln inhibited the proliferation, migration, and invasion of prostate cancer (PCa) cells in vitro and suppressed the growth of prostate cancer in vivo. PAGln notably increased the mRNA levels of CCNG2 in PCa cells. Importantly, the knockdown of CCNG2 weakened the effects of PAGln on PCa cells. Mechanistic studies revealed that PAGln could promote the phosphorylation of β-catenin by upregulating CCNG2, thereby inhibiting the Wnt/β-catenin signaling pathway.
    Conclusion: In summary, PAGln can effectively inhibit the proliferation, migration, and invasion of PCa by upregulating CCNG2 and suppressing the Wnt/β-catenin signaling pathway. These findings suggest that PAGln may serve as a promising therapeutic agent for prostate cancer.
    Keywords:  CCNG2; Wnt/β-catenin pathway; migration; phenylacetylglutamine; proliferation; prostate cancer
    DOI:  https://doi.org/10.3389/fphar.2025.1528058
  2. Cell Rep. 2025 Mar 26. pii: S2211-1247(25)00241-4. [Epub ahead of print]44(4): 115470
    Lipid-metabolism-focused CRISPR screens identify enzymes of the mevalonate pathway as essential for prostate cancer growth.
    Gio Fidelito, Izabela Todorovski, Leonie Cluse, Stephin J Vervoort, Renea A Taylor, Matthew J Watt.
      Dysregulated lipid metabolism plays an important role in prostate cancer, although the understanding of the essential regulatory processes in tumorigenesis is incomplete. We employ a CRISPR-Cas9 screen using a custom human lipid metabolism knockout library to identify essential genes for prostate cancer survival. Screening in three prostate cancer cell lines reveals 63 shared dependencies, with enrichment in terpenoid backbone synthesis and N-glycan biosynthesis. Independent knockout of key genes of the mevalonate pathway reduces cell proliferation. Further investigation focuses on NUS1, a subunit of cis-prenyltransferase required for dolichol synthesis. NUS1 knockout decreases tumor growth in vivo and viability in patient-derived xenograft (PDX)-derived organoids. Mechanistic studies reveal that loss of NUS1 promotes oxidative stress, lipid peroxidation and ferroptosis sensitivity, endoplasmic reticulum (ER) stress, and G1 cell-cycle arrest, and it dampens androgen receptor (AR) signaling, collectively leading to growth arrest. This study highlights the critical role of the mevalonate-dolichol-N-glycan biosynthesis pathway, particularly NUS1, in prostate cancer survival and growth.
    Keywords:  CP: Cancer; CP: Metabolism; CRISPR screen; cancer metabolism; lipid metabolism; prostate cancer
    DOI:  https://doi.org/10.1016/j.celrep.2025.115470
  3. J Biochem Mol Toxicol. 2025 Apr;39(4): e70210
    Silencing of PODXL2 Modulates Cell Viability and Tumor Immune Microenvironment of Prostate Cancer and Involves PI3K/AKT Pathway Inactivation.
    Yaowu Su, Liang Zhou, Qin Yu, Weihua Liu, Wei Liu.
      Prostate cancer (PCa) is one of the malignant tumors affecting men and is an important reason for the increase in male mortality worldwide. The pathogenesis of PCa is not fully understood. Thus, there is an urgent need to discover novel therapeutic targets to facilitate the development of effective anti-PCa strategies. Quantitative real-time PCR and Western blot were applied to detect the PODXL2 expressions in PCa tissues and cells. Progression-free survival of PCa patients was assessed using Kaplan-Meier survival analysis. The relevance between PODXL2 expressions and PCa clinical index was assessed with a Chi-square test. Cell infection, cell coculture system, Cell Counting Kit-8 assay, TUNEL staining, Transwell, analysis of PCa cell epithelial-mesenchymal transition (EMT) morphological changes, flow cytometry, and enzyme-linked immunosorbent assay were used for the analysis of PODXL2 functions in PCa. Meanwhile, the PODXL2 mechanism in PCa was dissected via Western blot, immunofluorescence analysis, Cell Counting Kit-8 assay, Transwell, and flow cytometry. Furthermore, PODXL2 impacts in PCa growth were examined in vivo using TUNEL staining, immunohistochemistry, and Western blot. PODXL2 expressions were raised in PCa tissues and cells, and PCa patients with high PODXL2 expressions owned poorer progression-free survival, and PODXL2 was interrelated to the TNM stage and distant metastasis of PCa. Interference with PODXL2 weakened PCa cell proliferation, invasion, EMT, and immune escape, while promoting PCa cell apoptosis. Furthermore, silencing PODXL2 reduced PCa cell proliferation, invasion, EMT, immune escape, and boosted cell apoptosis, which involved PI3K/AKT pathway inactivation. Meanwhile, PODXL2 knockdown reduced the tumor weight of PCa and promoted apoptosis in vivo. Interference with PODXL2 inhibited PCa cell proliferation, invasion, EMT, immune escape, enhanced cell apoptosis, and involved PI3K/AKT pathway inactivation.
    Keywords:  PI3K/AKT; PODXL2; prostate cancer; tumor immune microenvironment
    DOI:  https://doi.org/10.1002/jbt.70210
  4. BMC Cancer. 2025 Mar 21. 25(1): 521
    The combination of poly(ADP-ribose) polymerase inhibitor and statin inhibits the proliferation of human castration-resistant and taxane-resistant prostate cancer cells in vitro and in vivo.
    Yoshitaka Sekine, Daisuke Oka, Akira Ohtsu, Hiroshi Nakayama, Takeshi Miyao, Yoshiyuki Miyazawa, Seiji Arai, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuhiro Suzuki.
       BACKGROUND: Olaparib exhibits antitumor effects in castration-resistant prostate cancer patients with germline mutations in DNA repair genes. We previously reported that simvastatin reduced the expression of DNA repair genes in PC-3 cells. The efficacy of combination therapy using olaparib and simvastatin as "BRCAness" in castration-resistant and taxane-resistant prostate cancers was evaluated in this study.
    METHODS: PC-3, LNCaP, and 22Rv1 human prostate cancer cell lines were used to develop androgen-independent LNCaP cells (LNCaP-LA). mRNA and protein expression levels were evaluated by quantitative real-time polymerase chain reaction and western blot analysis, respectively. Cell viability was determined using the MTS assay and cell counts. All evaluations were performed on cells treated with simvastatin with or without olaparib.
    RESULTS: The mRNA levels of BRCA1, BRCA2, RAD51, FANCD2, FANCG, FANCA, BARD1, RFC3, RFC4, and RFC5, which are known DNA repair genes, were downregulated by simvastatin in androgen-independent prostate cancer cells, such as PC-3, LNCaP-LA, and 22Rv1 cells. In contrast, the expression of all these genes remained unchanged in androgen-dependent LNCaP cells following treatment with simvastatin. Furthermore, simvastatin increased the expression of above stated genes in normal prostate stromal cells (PrSC). The reduction in BRCA1 and BRCA2 expression following siRNA transfection increased the cytocidal effects of Olaparib in PC-3 and LNCaP-LA cells. The combination of olaparib and simvastatin further inhibited cell proliferation compared to monotherapy with either drug in PC-3, 22Rv1, and LNCaP-LA cells but not in PrSC cells. In a 22Rv1-derived mouse xenograft model, the combination of olaparib and simvastatin enhanced the inhibition of cell proliferation. Moreover, we established a 22Rv1 cell line with acquired resistance to Cabazitaxel (22Rv1-CR). In 22Rv1-CR cells, simvastatin also decreased the expression of BRCA1, BRCA2, and FANCA, and the combination of olaparib and simvastatin further enhanced the inhibition of cell proliferation compared with treatment with either of the drugs alone.
    CONCLUSIONS: Simvastatin altered the expression of several genes associated with DNA repair in castration-resistant and taxane-resistant prostate cancer cells. The combination of poly (ADP-ribose) polymerase inhibitors and drugs that decrease DNA repair gene expression can potentially affect castration-resistant and taxane-resistant prostate cancer growth.
    Keywords:  BRCA1; BRCA2; DNA repair gene; Olaparib; Prostate cancer; Simvastatin; Statin
    DOI:  https://doi.org/10.1186/s12885-025-13895-6
  5. J Xenobiot. 2025 Mar 18. pii: 45. [Epub ahead of print]15(2):
    Erioflorin and Erioflorin Acetate Induce Cell Death in Advanced Prostate Cancer Through ROS Increase and NF-κB Inhibition.
    Cecilia Villegas, Iván González-Chavarría, Viviana Burgos, Jaime R Cabrera-Pardo, Bernd Schmidt, Cristian Paz.
      Germacranes are a type of sesquiterpene lactones with anti-inflammatory and cytotoxic properties against cancer cell lines. In this in vitro study, erioflorin and erioflorin acetate were isolated and purified from the leaves of Podanthus mitiqui Lindl (Mitique or Mitriu), a shrub endemic to Chile and traditionally used in Mapuche medicine to treat urinary and digestive disorders. Their effects on advanced prostate cancer cell lines (DU-145 and 22Rv1) were evaluated. Cytotoxicity was assessed using real-time cell death and clonogenic assays. Apoptosis was determined by measuring reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), and apoptotic cell percentage through flow cytometry. Gene expression of BAX and BCL-2 was analyzed via RT-qPCR, while NF-κB activation was studied in DU-145 cells and human monocytic NF-κB reporter assays using LPS stimulation and alkaline phosphatase activity quantification. Erioflorin acetate exhibited the highest cytotoxicity, with IC50 values of 35.1 µM (22Rv1) and 27.3 µM (DU-145), compared to erioflorin, which had IC50 values of 50.3 µM and 56.5 µM, respectively. Both compounds increased ROS levels, reduced ΔΨm, and induced apoptosis. RT-qPCR analysis revealed that erioflorin elevated the BAX/BCL-2 ratio, and both compounds inhibited NF-κB activation by preventing IκBα phosphorylation. In conclusion, the findings demonstrate that erioflorin and erioflorin acetate exert significant in vitro cytotoxic and cytostatic effects on prostate cancer cells, supporting their potential as natural candidates for prostate cancer therapy.
    Keywords:  NF-κB signaling; Podanthus mitiqui; cytotoxicity; erioflorin; germacrane sesquiterpene lactones; prostate cancer
    DOI:  https://doi.org/10.3390/jox15020045
  6. Drug Dev Res. 2025 Apr;86(2): e70078
    Inhibition of Steroidogenesis in Prostate Cancer Cells by Both a Natural and Another Synthetic Steroid.
    Marisa Cabeza, Karla Mejía, Fernando García, Ivonne Heuze, Miguel Morales, Mauricio Rodríguez-Dorantes.
      Studies suggest that vegetarians and Asians have lower mortality rates from prostate cancer compared to men who follow a Western diet. β-sitosterol, a key compound of plant-based diets, has been found to induce significant changes in the ultrasonic structure of the prostatic adenomas, making it a promising candidate for further prostate cancer research. Consequently, we investigated the potential of β-sitosterol and the synthetic derivative 2 as potent inhibitors of androgen synthesis, a critical process for the growth and survival of prostate tumor LNCaP cells. Solubilized LNCaP microsomes were used as a source of SRD5A1 and AKR1C3 to monitor androgen synthesis from labeled androstenedione, both in the presence and absence of β-sitosterol or 2. Furthermore, the effect of these steroids on LNCaP viability was determined using the MTT method. Our findings revealed significant insights into the androgen synthesis pathways in LNCaP cells. The most efficient metabolic route for dihydrotestosterone formation was the conversion of androstenedione to 5α-androstanedione rather than from testosterone in LNCaP. This conclusion is supported by the Vmax values for 5α-androstanedione formation (271.05 ± 5.0 ng/mg protein/min) and the Vmax of testosterone formation (80.1 ± 8.0 ng/mg protein/min). Both β-sitosterol and 2 demonstrated substantial inhibitory effects of these enzymes for dihydrotestosterone formation and significantly reduced cell viability, highlighting their therapeutic potential. These findings enhance our understanding of the inhibitory effects of β-sitosterol and 2 on LNCaP cells and suggest their promising application in the treatment of prostate cancer.
    Keywords:  17β‐hydroxysteroid dehydrogenase activity; LNCaP cells proliferation; androstane derivative; type 1 5α‐reductase activity; β‐sitosterol
    DOI:  https://doi.org/10.1002/ddr.70078
  7. Int J Mol Sci. 2025 Mar 12. pii: 2558. [Epub ahead of print]26(6):
    Lanatoside C Inhibits Proliferation and Induces Apoptosis in Human Prostate Cancer Cells Through the TNF/IL-17 Signaling Pathway.
    Sisi Huang, Dongyan Huang, Yangtao Jin, Congcong Shao, Xin Su, Rongfu Yang, Juan Jiang, Jianhui Wu.
      Prostate cancer remains a leading cause of cancer-related morbidity and mortality among men globally, with limited therapeutic options for advanced and metastatic disease. The therapeutic potential of natural compounds has attracted increasing attention in cancer treatment. Lanatoside C (Lan C), a cardiac glycoside derived from Digitalis lanata, has demonstrated promising anticancer activity across various cancer types. However, its role and mechanisms in prostate cancer remain underexplored. In this study, evidence shows that Lan C significantly inhibits the proliferation of prostate cancer cells, as demonstrated by reduced cell viability, suppressed colony formation, and G2/M cell cycle arrest. Additionally, Lan C promotes apoptosis and inhibits the migration and invasion of prostate cancer cells. Mechanistically, transcriptomic analysis identified differentially expressed genes, which were further validated at both the mRNA and protein levels. Our findings suggest that Lan C exerts its effects by modulating the TNF/IL-17 signaling pathway, influencing the tumor microenvironment and regulating key processes involved in tumor progression, immune response, and apoptosis.
    Keywords:  Lanatoside C; cardiac glycosides; interleukin-17; prostate cancer; tumor necrosis factor
    DOI:  https://doi.org/10.3390/ijms26062558
  8. Sci Rep. 2025 Mar 25. 15(1): 10272
    The MicroRNA miR-454 and the mediator complex component MED12 are regulators of the androgen receptor pathway in prostate cancer.
    Juan Guzman, Martin Hart, Katrin Weigelt, Angela Neumann, Achim Aigner, Chiara Andolfi, Florian Handle, Stefanie Rheinheimer, Ulrike Fischer, Uta D Immel, Verena Lieb, Eckart Meese, Zoran Culig, Bernd Wullich, Helge Taubert, Sven Wach.
      Prostate cancer that is resistant to anti-androgen treatment, such as enzalutamide, represents a therapeutic challenge. To study their molecular and functional features, the enzalutamide-resistant PCa cell lines LNCaP Abl EnzR and DuCaP EnzR constitute valuable in vitro models. In this work, we explored two different strategies for reducing AR/AR-V7/c-Myc. MED12 knockdown decreased the protein expression of AR, AR-V7 and c-Myc. Similarly, we identified AR and AR-V7 as targets of miR-454-3p. Concomitantly, the transfection of synthetic miR-454-3p reduced the protein expression of AR in both EnzR cell lines and that of c-Myc and AR-V7 in the DuCaP EnzR cell line without affecting MED12. Despite these similar molecular effects, differences were observed at the cellular level, with siMED12, but not miR-454, reducing cell viability, and no additive effects upon double treatment were observed. Taken together, the results of our study suggest MED12 as a potential target for future PCa treatment in conjunction with enzalutamide resistance. Furthermore, miR-454-3p, which directly targets AR and AR-V7 and indirectly influences c-Myc protein expression, reveals new molecular mechanisms in PCa biology.
    Keywords:  Androgen receptor; Androgen receptor splice variant 7; Cell viability; MED12; MiRNA; Prostate cancer; Protein expression; c-Myc
    DOI:  https://doi.org/10.1038/s41598-025-95250-0
  9. Biochem Biophys Rep. 2025 Jun;42 101959
    Characterization of lncRNA-protein interactions associated with Prostate cancer and Androgen receptors by molecular docking simulations.
    Barkha Khilwani, Bhumandeep Kour, Nidhi Shukla, Sugunakar Vuree, Abdul S Ansari, Nirmal K Lohiya, Prashanth Suravajhala, Renuka Suravajhala.
      Long non-coding RNA (lncRNAs) are known to be implicated in pathogenesis of a broad spectrum of malignancies. These are found to have a significant role as signal transduction mediators in cancer signaling pathways. Prostate Cancer (PCa) is emerging with increasing cases worldwide even as advanced approaches in clinical diagnosis and treatment of PCa are still challenging to address. To enhance patient stratification, there is an indefatigable need to understand risk that can allow new approaches of treatment based on prognosis. While PCa is known to have mediated androgen receptor (AR) stimulation, the latter plays a critical role in regulating transcription of genes via nuclear translocation which in turn leads to response to androgens. LncRNAs have been implicated in developing clinical diagnostic and prognostic biomarkers in a broad spectrum of cancers. In our present study, 12 lncRNAs identified from clinical samples from our erstwhile PCa patients were docked with PCa and AR targeted 36 proteins. We identified three lncRNAs, viz. SCARNA10, NPBWR1, ANKRD20A9P are common between the targeted proteins and discern that SCARNA10 lncRNA could serve as a prognostic signature for PCa and AR biogenesis. We also sought to check the coding potential of interfacial residues associated with lncRNA docking sites.
    Keywords:  5α-dihydrotestosterone (DHT); Androgen receptor; Differentially expressed genes; Long non-coding RNAs; Molecular docking; Prostate cancer
    DOI:  https://doi.org/10.1016/j.bbrep.2025.101959
  10. Eur J Nucl Med Mol Imaging. 2025 Mar 27.
    Dual-tracer PET/CT for lung and prostate cancer: 18F-FDG and 18F-PSMA-1007.
    Haijun Li, Lifeng Li, Dechang Peng.
      
    DOI:  https://doi.org/10.1007/s00259-025-07226-x
  11. Future Oncol. 2025 Mar 26. 1-14
    Contemporary real-world treatment in metastatic hormone-sensitive prostate cancer: US, four European countries, and UK.
    Peter J Goebell, Stephanie Chen, Jay Jhaveri.
       AIM: To characterize contemporary global real-world metastatic hormone-sensitive prostate cancer (mHSPC) treatment, guideline concordance, trends, and potential trend drivers.
    MATERIALS AND METHODS: Retrospective data from the Ipsos Global Oncology Monitor database for the United States, Germany, France, Spain, Italy, and the United Kingdom were used for descriptive analysis of mHSPC patients, treating physicians, and treatment utilization. Statistical testing of differences among treatment cohorts for the final study period was conducted.
    RESULTS: Of 15,662 total mHSPC patients across countries (2019-2024), the 1404 patients from the most recent and relevant study period (August 2023-January 2024) had an average age of 72-74 years, good baseline functioning, high-risk prostate cancer features, and cardiometabolic conditions as top comorbidities. Treatment mostly occurred in hospital/institutional settings and urban locales by oncologists versus urologists. Monotherapy androgen deprivation therapy (mADT) use declined while use of novel androgen receptor inhibitor (nARI) combination therapies, especially doublets, increased. Concordance between real-world and guideline-recommended treatment varied by country, ranging from 43.8% to 61.6%.
    CONCLUSIONS: Concordance with guidelines improved globally driven by nARIs. Persistent use of mADT, a non-guideline-recommended therapy, indicates physicians' concern about the safety and trade-offs with current options. New therapies delivering greater net benefits are needed, along with education on guideline adherence.
    Keywords:  Androgen antagonists, therapeutic use; antineoplastic agents, hormonal, therapeutic use; antineoplastic combined chemotherapy protocols, therapeutic use; guideline adherence; practice patterns, physicians’ trends; prostatic neoplasms, drug therapy; real-world evidence; urologic/prostate
    DOI:  https://doi.org/10.1080/14796694.2025.2481024
  12. Discov Oncol. 2025 Mar 23. 16(1): 375
    Gut microbiome, dietary habits, and prostate cancer: a two-step Mendelian randomization revealing the causal associations.
    Junhua Guo, Ting Huang, Heran Zhou.
       BACKGROUND: Recent studies suggest that diet fizzy drinks may contribute to prostate cancer (PCa) development. However, the causal effects between diet fizzy drinks and PCa and whether gut microbiota (GM) act as a mediator remain unclear.
    METHODS: We conducted two-sample Mendelian Randomization (MR) analyses utilizing large-scale genome-wide association studies (GWAS) data from the UK Biobank, the MiBioGen consortium, and PCa-related datasets. The inverse-variance weighted (IVW) method was used to evaluate the causal effects of GM and dietary preferences on PCa risk. A mediation analysis was performed to investigate whether GM mediates the relationship between dietary factors and PCa risk.
    RESULTS: Diet fizzy drink consumption was causally associated with reduced PCa risk (OR = 0.83, 95% CI: 0.70-0.99, P = 0.041) and decreased abundance of PCa-risk-related GM taxa (Negativicutes and Selenomonadales). Mediation analysis did not reveal a statistically significant mediation effect, with a mediation proportion of 16% (95% CI: - 0.06-0.37, P = 0.13).
    CONCLUSION: Consumption of diet fizzy drinks may reduce the risk of PCa, potentially through modulation of the GM; however, further studies are required to confirm these findings and clarify underlying mechanisms.
    Keywords:  Diet fizzy drinks; Genome-wide association studies; Gut microbiome; Mendelian randomization; Prostate cancer
    DOI:  https://doi.org/10.1007/s12672-025-02172-4
  13. J Biol Chem. 2025 Mar 25. pii: S0021-9258(25)00299-6. [Epub ahead of print] 108450
    Low dose Taxol causes mitochondrial dysfunction in actively respiring cancer cells.
    Rozhin Penjweini, Katie A Link, Shureed Qazi, Nikhil Mattu, Adam Zuchowski, Alexandra Vasta, Dan L Sackett, Jay R Knutson.
      Mitochondrial oxygen consumption, dynamics and morphology play roles in the occurrence, development and drug resistance of cancer; thus they are main targets for many anticancer drugs. Increased mitochondrial oxygen consumption and impaired oxygen delivery creates hypoxia, which influences the balance of metabolic co-factors for biogenesis, disease progression and response to therapeutics. We therefore investigated the effects of Taxol, a well-known anticancer drug, on mitochondrial respiration (principally via a measure of oxidative phosphorylation (OXPHOS) versus glycolysis), morphology and dynamics. The concomitant effects of Taxol on mitochondrial adenosine triphosphate (ATP) and reactive oxygen species (ROS) production, mitochondrial membrane potential, radical-induced formation of carbonyl groups, mitochondrial release of cytochrome c, as well as cell cycle were investigated. Cells used in this study include: A549 (non-small cell lung epithelial cancer cell line), A549-ρ0 (mitochondrial DNA-depleted derivative of A549), and BEAS-2B (a non-cancer cell line derived from normal bronchial epithelium), as well as PC3 (prostate cancer) and HepG2 (hepatocellular carcinoma); these cell lines are known to have disparate metabolic profiles. Using a multitude of fluorescence-based measurements, we show that Taxol, even at a low dose, still adversely effects mitochondria of actively respiring (aerobic) cancer cells. We find an increase in mitochondrial ROS and cytochrome c release, suppression of ATP production and OXPHOS, fragmentation of the mitochondrial network and disruption of mitochondria-microtubule linkage. We find these changes in oxidative, but not glycolytic, cancer cells. Non-cancer cells, which are oxidative, do not show these changes.
    Keywords:  Low-dose Taxol; Mitochondrial metabolism; OXPHOS; morphology and dynamics
    DOI:  https://doi.org/10.1016/j.jbc.2025.108450
  14. Biology (Basel). 2025 Mar 04. pii: 256. [Epub ahead of print]14(3):
    Uncovering New Biomarkers for Prostate Cancer Through Proteomic and Network Analysis.
    Rossana Rossi, Elena Monica Borroni, Ishak Yusuf, Andrea Lomagno, Mohamed A A A Hegazi, Pietro Luigi Mauri, Fabio Grizzi, Gianluigi Taverna, Dario Di Silvestre.
       BACKGROUND: Prostate cancer (PCa), is the second most prevalent solid tumor among men worldwide (7.3%), and the leading non-skin cancer in USA where it represents 14.9% of all new cancer cases diagnosed in 2024. This multifactorial disease exhibits substantial variation in incidence and mortality across different ethnic groups and geographic regions. Although prostate-specific antigen (PSA) remains widely used as a biomarker for PCa, its limitations reduce its effectiveness for accurate detection. Consequently, finding molecules that can either complement PSA and other biomarkers is a major goal in PCa research.
    METHODS: Urine samples were collected from healthy donors (n = 5) and patients with low- and high-risk PCa (4 and 7 subjects, respectively) and were analyzed using proteomic data-derived systems and biology approaches. The most promising proteins were further investigated by means of The Cancer Genome Atlas (TCGA) database to assess their associations with clinical and histopathological characteristics in a larger in silico patient population.
    RESULTS: By evaluating the variations in the urinary proteome as a mirror of the changes occurring in prostate tumor tissue, components of complement and coagulation cascades and glutathione metabolism emerged as hallmarks of low- and high-risk PCa patients, respectively. Moreover, our integrated approach highlighted new potential biomarkers, including CPM, KRT8, ITIH2, and RCN1.
    CONCLUSIONS: The good overlap of our results with what is already reported in the literature supports the new findings in the perspective of improving the knowledge on PCa. Furthermore, they increase the panel of biomarkers that could enhance PCa management. Of course, further investigations on larger patient cohorts are required.
    Keywords:  TCGA; hubs; network analysis; prostate cancer; proteomics; urine
    DOI:  https://doi.org/10.3390/biology14030256
  15. J Exp Clin Cancer Res. 2025 Mar 24. 44(1): 105
    Blood-based detection of MMP11 as a marker of prostate cancer progression regulated by the ALDH1A1-TGF-β1 signaling mechanism.
    Ielizaveta Gorodetska, Vasyl Lukiyanchuk, Marta Gawin, Myroslava Sliusar, Annett Linge, Fabian Lohaus, Tobias Hölscher, Kati Erdmann, Susanne Fuessel, Angelika Borkowetz, Anna Wojakowska, Daniel Fochtman, Mark Reardon, Ananya Choudhury, Yasmin Antonelli, Aldo Leal-Egaña, Ayse Sedef Köseer, Uğur Kahya, Jakob Püschel, Andrea Petzold, Daria Klusa, Claudia Peitzsch, Romy Kronstein-Wiedemann, Torsten Tonn, Lukasz Marczak, Christian Thomas, Piotr Widłak, Monika Pietrowska, Mechthild Krause, Anna Dubrovska.
       BACKGROUND: Prostate cancer (PCa) is the second most common type of tumor diagnosed in men and the fifth leading cause of cancer-related death in male patients. The response of metastatic disease to standard treatment is heterogeneous. As for now, there is no curative treatment option available for metastatic PCa, and the clinical tests capable of predicting metastatic dissemination and metastatic response to the therapies are lacking. Our recent study identified aldehyde dehydrogenases ALDH1A1 and ALDH1A3 as critical regulators of PCa metastases. Still, the exact mechanisms mediating the role of these proteins in PCa metastatic dissemination remain not fully understood, and plasma-based biomarkers of these metastatic mechanisms are not available.
    METHODS: Genetic silencing, gene overexpression, or treatment with different concentrations of the retinoic acid (RA) isomers, which are the products of ALDH catalytic activity, were used to modulate the interplay between retinoic acid receptors (RARs) and androgen receptor (AR). RNA sequencing (RNAseq), reporter gene assays, and chromatin immunoprecipitation (ChIP) analysis were employed to validate the role of RARs and AR in the regulation of the transforming growth factor-beta 1 (TGFB1) expression. Gene expression levels of ALDH1A1, ALDH1A3, and the matrix metalloproteinase 11 (MMP11) and their correlation with pathological parameters and clinical outcomes were analysed by mining several publicly available patient datasets as well as our multi-center transcriptomic dataset from patients with high-risk and locally advanced PCa. The level of MMP11 protein was analysed by enzyme-linked immunosorbent assay (ELISA) in independent cohorts of plasma samples from patients with primary or metastatic PCa and healthy donors, while plasma proteome profiles were obtained for selected subsets of PCa patients.
    RESULTS: We could show that ALDH1A1 and ALDH1A3 genes differently regulate TGFB1 expression in a RAR- and AR-dependent manner. We further observed that the TGF-β1 pathway contributes to the regulation of the MMPs, including MMP11. We have confirmed the relevance of MMP11 as a promising clinical marker for PCa using several independent gene expression datasets. Further, we have validated plasma MMP11 level as a prognostic biomarker in patients with metastatic PCa. Finally, we proposed a hypothetical ALDH1A1/MMP11-related plasma proteome-based prognostic signature.
    CONCLUSIONS: TGFB1/MMP11 signaling contributes to the ALDH1A1-driven PCa metastases. MMP11 is a promising blood-based biomarker of PCa progression.
    Keywords:  ALDH1A1; Liquid biopsy; MMP11; Metastasis; Prostate cancer; TGF-β1
    DOI:  https://doi.org/10.1186/s13046-025-03299-6
  16. BMC Urol. 2025 Mar 27. 25(1): 61
    A novel equation synthesis for estimating resting energy expenditure in prostate cancer patients.
    Nilüfer Acar Tek, Tevfik Koçak, Süleyman Yeşil, Tevfik Sinan Sözen.
       BACKGROUND: An accurate calculation of energy expenditure (REE) is necessary for estimating energy needs in malign prostate cancer. The purpose of this research was to evaluate the accuracy of the established novel equation for predicting REE in malign and benign prostate patients versus the accuracy of the previously used predictive equations based on REE measured by indirect calorimetry.
    METHODS: The study was conducted as a cross-sectional case-control study and between December 2020 and May 2021 with 40 individuals over the age of 40 who applied to the Urology Clinic of Gazi University Faculty of Medicine. Subjects with 41 malign prostate and 42 benign prostate patients were both over the age of 40 (65.3 ± 6.30 years) and recruited for the study. Cosmed-FitMate GS Indirect Calorimetry with Canopyhood (Rome, Italy) was used to measure REE. A full body composition analysis and anthropometric measurements were taken.
    CLINICAL TRIAL NUMBER: Not applicable.
    RESULTS: Malign prostate group PSA Total and measured REE values (4.93 ± 5.44 ng/ml, 1722.9 ± 272.69 kcal/d, respectively) were statistically significantly higher than benign group (1.76 ± 0.73 ng/ml, 1670.5 ± 266.76 kcal/d, respectively) (p = 0.022). Malign prostate group (MPG) and benign prostate group (BPG) have the highest percentage of the accurate prediction value of Eq. 80.9% (novel equation MPG) and 64.2% (novel equation BPG). The bias of the equations varied from - 36.5% (Barcellos II Equation) to 19.2% (Mifflin-St. Jeor equation) for the malign prostate group and varied from - 41.1% (Barcellos II Equation) to 17.7% (Mifflin-St. Jeor equation) in the benign prostate group. The smallest root mean squared error (RMSE) values in the malign and benign prostate groups were novel equation MPG (149 kcal/d) and novel equation BPG (202 kcal/d). The new specific equation for malign prostate cancer: REE = 3192,258+ (208,326* body weight (WT)) - (20,285* height (HT)) - (187,549* fat free mass (FFM)) - (203,214* fat mass (FM)) + (4,194* prostate specific antigen total (PSAT)). The new specific equation for the benign prostate group is REE = 615,922+ (13,094*WT). Bland-Altman plots reveal an equally random distribution of novel equations in the malign and benign prostate groups.
    CONCLUSIONS: Previously established prediction equations for REE may be inconsistent. Utilising the PSAT parameter, we formulated novel energy prediction equations specific to prostate cancer. In any case, the novel predictive equations enable clinicians to estimate REE in people with malign and benign prostate groups with sufficient and most acceptable accuracy.
    Keywords:  Indirect calorimetry; Novel predictive equations; Prostate cancer; Resting energy expenditure
    DOI:  https://doi.org/10.1186/s12894-024-01648-9
  17. J Bone Oncol. 2025 Apr;51 100667
    Zoledronic acid in metastatic castrate-sensitive prostate cancer: A state-of-the-art review.
    Nahed Damaj, Tala Najdi, Samah Seif, Nicolas Nakouzi, Joseph Kattan.
      Prostate cancer is the most common cancer in men in developed countries. Despite its slow growing pattern, metastatic disease to bone occurs and results in a significant number of deaths. Since more than eight decades, the classical androgen deprivation therapy (ADT) leads to clinical response in most patients with metastatic castration-sensitive prostate cancer (mCSPC). Moving backward docetaxel and androgen receptor pathway inhibitors (ARPI) from castrate-resistant setting to castrate sensitive setting improves overall survival (OS) compared to ADT alone. Recently, studies suggested that triplet therapy by adding ARPIs such as abiraterone acetate or darolutamide to ADT + docetaxel is more effective than ADT/docetaxel alone in patients with high-volume mCSPC. Although the scientific progress during the last decade, has led to improvements in outcome for patients with mCSPC, there are still several areas impacting daily practice, for which high-level evidence is lacking, especially for adding monthly zoledronic acid in this setting. We structured this review by conducting a comprehensive analysis of the existing literature. This manuscript reviews both the benefits and potential harms of zoledronic acid in the treatment of mCSPC and provides conclusions on the criteria for its use, and the possible use of alternative bone protecting agents (BPA).
    Keywords:  Bisphosphonates; Bone fracture; Bone metastasis; Metastatic castrate sensitive prostate cancer; Zoledronic acid
    DOI:  https://doi.org/10.1016/j.jbo.2025.100667
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