{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:58:57Z","timestamp":1760151537350,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Prostate cancer is a common cause of cancer death in men. In advanced stages of prostate cancer, androgen deprivation therapy (ADT) is initiated. Despite ADT, prostate cancers invariably progress to become androgen independent. A growing body of evidence implicates iron dysmetabolism in prostate cancer progression. A bioactive peptide-rich salmon protein hydrolysate (SPH) has previously been demonstrated to modulate iron homeostatic mechanisms. In the present study, the anticancer effect of SPH and bicalutamide co-treatment on LNCaP and PC3 prostate cancer cell proliferation was investigated. Our results found that SPH potentiates the anti-proliferative effect of bicalutamide in a dose-dependent manner for both cell lines. In the presence of 160 \u00b5g\/mL SPH, co-treatment with 1.0 \u00b5M bicalutamide decreased LNCaP cells\u2019 relative colony survival from 25% (1.0 \u00b5M bicalutamide monotreatment) to 2% after culturing for 12 days. For PC3 cells, the relative colony survival diminished from 52% (10.0 \u00b5M bicalutamide) to 32% at an SPH concentration of 160 \u00b5g\/mL. Gene expression profiling, employing quantitative real-time PCR, revealed that the inhibitory effects were related to significant FTH1 up-regulation with a concomitant TFRC down-regulation. In conclusion, our results provide in vitro evidence that SPH potentiates the growth inhibitory effect of bicalutamide on prostate cancer cells by modulating iron homeostasis mechanisms.<\/jats:p>","DOI":"10.3390\/md20040228","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T21:41:30Z","timestamp":1648590090000},"page":"228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Salmon Protein Hydrolysate Potentiates the Growth Inhibitory Effect of Bicalutamide on Human Prostate Cancer Cell Lines LNCaP and PC3 by Modulating Iron Homeostasis"],"prefix":"10.3390","volume":"20","author":[{"given":"Christian","family":"Bjerknes","sequence":"first","affiliation":[{"name":"Hofseth Biocare, Kipervikgata 13, 6003 \u00c5lesund, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bomi","family":"Framroze","sequence":"additional","affiliation":[{"name":"Hofseth Biocare, Kipervikgata 13, 6003 \u00c5lesund, Norway"},{"name":"GPH Biotech LLC, 1455 Adams Drive, Menlo Park, CA 94025, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crawford","family":"Currie","sequence":"additional","affiliation":[{"name":"Hofseth Biocare, Kipervikgata 13, 6003 \u00c5lesund, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0658-0061","authenticated-orcid":false,"given":"Caroline Hild Hakv\u00e5g","family":"Pettersen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, 7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karol","family":"Axcrona","sequence":"additional","affiliation":[{"name":"Department of Urology, Akershus University Hospital, 1478 L\u00f8renskog, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erland","family":"Hermansen","sequence":"additional","affiliation":[{"name":"Hofseth Biocare, Kipervikgata 13, 6003 \u00c5lesund, Norway"},{"name":"Department of Clinical Medicine, University of Bergen, 5007 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0140-6736(21)00950-8","article-title":"Prostate cancer","volume":"398","author":"Sandhu","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/mnfr.200700511","article-title":"International epidemiology of prostate cancer: Geographical distribution and secular trends","volume":"53","author":"Baade","year":"2009","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3322\/canjclin.22.4.232","article-title":"Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate","volume":"22","author":"Huggins","year":"1972","journal-title":"CA Cancer J. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1464-410X.2012.11215.x","article-title":"Androgen deprivation therapy: Past, present and future","volume":"109","author":"Crawford","year":"2012","journal-title":"BJU Int."},{"doi-asserted-by":"crossref","unstructured":"Ehsani, M., David, F.O., and Baniahmad, A. (2021). Androgen Receptor-Dependent Mechanisms Mediating Drug Resistance in Prostate Cancer. Cancers, 13.","key":"ref_6","DOI":"10.3390\/cancers13071534"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.cell.2018.06.039","article-title":"Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer","volume":"174","author":"Quigley","year":"2018","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/S0090-4295(02)01576-5","article-title":"Antiandrogen monotherapy: Indications and results","volume":"60","author":"Iversen","year":"2002","journal-title":"Urology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/CCO.0000000000000624","article-title":"Recent progress in treating advanced prostate cancer","volume":"32","author":"Gourdin","year":"2020","journal-title":"Curr. Opin. Oncol."},{"doi-asserted-by":"crossref","unstructured":"Leli\u00e8vre, P., Sancey, L., Coll, J.-L., Deniaud, A., and Busser, B. (2020). Iron Dysregulation in Human Cancer: Altered Metabolism, Biomarkers for Diagnosis, Prognosis, Monitoring and Rationale for Therapy. Cancers, 12.","key":"ref_10","DOI":"10.20944\/preprints202010.0447.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"778492","DOI":"10.3389\/fonc.2021.778492","article-title":"The Role of Iron in Cancer Progression","volume":"11","author":"Guo","year":"2021","journal-title":"Front. Oncol."},{"doi-asserted-by":"crossref","unstructured":"Zhou, L., Zhao, B., Zhang, L., Wang, S., Dong, D., Lv, H., and Shang, P. (2018). Alterations in Cellular Iron Metabolism Provide More Therapeutic Opportunities for Cancer. Int. J. Mol. Sci., 19.","key":"ref_12","DOI":"10.3390\/ijms19051545"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/his.13847","article-title":"Transferrin receptor 1 overexpression is associated with tumour de-differentiation and acts as a potential prognostic indicator of hepatocellular carcinoma","volume":"75","author":"Adachi","year":"2019","journal-title":"Histopathology"},{"key":"ref_14","first-page":"916","article-title":"Transferrin receptor 1 in cancer: A new sight for cancer therapy","volume":"8","author":"Shen","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6387","DOI":"10.1158\/1078-0432.CCR-20-3182","article-title":"Iron Induces Cell Death and Strengthens the Efficacy of Antiandrogen Therapy in Prostate Cancer Models","volume":"26","author":"Bordini","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16497","DOI":"10.1038\/srep16497","article-title":"Regulation of iron homeostasis by the p53-ISCU pathway","volume":"5","author":"Funauchi","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1074\/mcp.M113.037176","article-title":"Ferritin heavy chain in triple negative breast cancer: A favorable prognostic marker that relates to a cluster of differentiation 8 positive (CD8+) effector T-cell response","volume":"13","author":"Liu","year":"2014","journal-title":"Mol. Cell. Proteom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1093\/nar\/gkx1248","article-title":"A FTH1 gene:pseudogene:microRNA network regulates tumorigenesis in prostate cancer","volume":"46","author":"Chan","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/pros.21383","article-title":"PC3 is a cell line characteristic of prostatic small cell carcinoma","volume":"71","author":"Tai","year":"2011","journal-title":"Prostate"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.4155\/fmc-2020-0140","article-title":"The world of cell penetrating: The future of medical applications","volume":"12","author":"Falanga","year":"2020","journal-title":"Future Med. Chem."},{"key":"ref_21","first-page":"398","article-title":"An in-vitro study on the regulation of oxidative protective genes in human gingival and intestinal epithelial cells after treatment with salmon protein hydrolysate peptides","volume":"8","author":"Framroze","year":"2018","journal-title":"Funct. Foods Health Dis."},{"key":"ref_22","first-page":"2","article-title":"A Placebo-Controlled Study of the Impact of Dietary Salmon Protein Hydrolysate Supplementation in Increasing Ferritin and Hemoglobin Levels in Iron-Deficient Anemic Subjects","volume":"5","author":"Framroze","year":"2015","journal-title":"J. Nutr. Food Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1158\/0008-5472.CAN-14-2465","article-title":"Hepcidin regulation in prostate and its disruption in prostate cancer","volume":"75","author":"Tesfay","year":"2015","journal-title":"Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3101","DOI":"10.1002\/2211-5463.13303","article-title":"Ferritin heavy chain (FTH1) exerts significant antigrowth effects in breast cancer cells by inhibiting the expression of c-MYC","volume":"11","author":"Ali","year":"2021","journal-title":"FEBS Open bio"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.cell.2010.06.028","article-title":"Two to Tango: Regulation of Mammalian Iron Metabolism","volume":"142","author":"Hentze","year":"2010","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.cofs.2021.03.005","article-title":"Bioaccessibility of bioactive peptides: Recent advances and perspectives","volume":"39","author":"Udenigwe","year":"2021","journal-title":"Curr. Opin. Food Sci."},{"doi-asserted-by":"crossref","unstructured":"Pavlicevic, M., Maestri, E., and Marmiroli, M. (2020). Marine Bioactive Peptides\u2014An Overview of Generation, Structure and Application with a Focus on Food Sources. Mar. Drugs, 18.","key":"ref_27","DOI":"10.3390\/md18080424"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1158\/1535-7163.MCT-08-0823","article-title":"Interleukin-6 increases prostate cancer cells resistance to bicalutamide via TIF2","volume":"8","author":"Feng","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/pcan.2012.16","article-title":"Metformin enhances the antiproliferative and apoptotic effect of bicalutamide in prostate cancer","volume":"15","author":"Colquhoun","year":"2012","journal-title":"Prostate Cancer Prostatic Dis."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/4\/228\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:44:39Z","timestamp":1760136279000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/20\/4\/228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,28]]},"references-count":29,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["md20040228"],"URL":"https:\/\/doi.org\/10.3390\/md20040228","relation":{},"ISSN":["1660-3397"],"issn-type":[{"type":"electronic","value":"1660-3397"}],"subject":[],"published":{"date-parts":[[2022,3,28]]}}}