Prostate specific antigen reduction following statin therapy: Mechanism of action and review of the literature

Abstract

SummaryProstate specific antigen (PSA) is a serine protease that is exclusively produced in the prostate, and its detection is the only laboratory test available for screening men for prostate cancer (PC). The interpretation of the assay is difficult since it is specific for prostate tissue and cellular growth, but not for PC. Pharmacologic therapy for hyperlipidemia, such as statins, may influence prostate cellular growth and subsequently PSA levels in patients. Dysregulated cellular growth in the prostate is mediated by inhibiting the rate-limiting pathway step in cholesterol synthesis, thereby decreasing isoprenylate intermediates, decreasing cholesterol rich cellular membrane domains, and down-regulating androgen and estrogen receptors. Statins, with variable efficacy, have been previously shown to inhibit cellular inflammation, angiogenesis, proliferation, migration/adhesion, and invasion, while promoting apoptosis in prostate cells by inhibiting the conversion of HMG-CoA to mevalonate. An individual statin's molecular structure, need for enzymatic conversion, bioavailability, and peripheral tissue concentration may partially account for differing properties. By inhibiting prostatic cellular growth and promoting apoptosis, statins may subsequently decrease PSA levels, an effect recently observed in cohorts. There is scientific and clinical evidence supporting the observations that statins are associated with an overall reduction in serum PSA in men, when used for greater than 6 months, and especially when used for greater than 2 years. 2010 IUBMB IUBMB Life, 62(8): 584-590, 2010

Synergistic Simvastatin and Metformin Combination Chemotherapy for Osseous Metastatic Castration-Resistant Prostate Cancer

“…Individual treatment with SIM or MET did not significantly decrease GU tract weight or ventral prostate/primary tumor proliferative index compared to untreated controls (Figure 4B, C). However, the SIM group demonstrated a significant decrease in the plasma PSA versus untreated control, consistent with previous reports (24, 48); MET treatment did not affect plasma PSA (Figure 4D). SIM and MET individual treatment led to slightly reduced cachexia incidence (13% and 11% of mice, respectively).…”

Crude extract of Euphorbia formosana inhibits the migration and invasion of DU145 human prostate cancer cells: The role of matrix metalloproteinase-2/9 inhibition via the MAPK signaling pathway

“…Prostate cancer has a poor prognosis due in part to tumor invasion and migration. The propensity of prostate cancer cells to metastasize to the bone greatly reduces the effectiveness of available treatment options (7)(8)(9).…”

Prostate-specific antigen levels in hypertensive patients suffering from a non-ST elevation myocardial infarction or a new-onset atrial fibrillation

“…PSA levels gradually change with age and we prefer to use the percentage of age-specific PSA ranges (a.s. PSA) instead of the simple PSA levels [26]. None of the final population was in treatment with 5-alpha reductase inhibitor and/or cardiac glycosides and/or International Journal of Cardiology 158 (2012) 380-382 nonsteroidal anti-inflammatory drug (including acetylsalicylic acid(asa) and/or statins and/or thiazide diuretics and/or paracetamol and/or calcium channel blockers because their effect on serum PSA levels reduction [27][28][29][30][31][32][33].…”