OBJECTIVES: To investigate why statin users display a noticeable decline in prostate specific antigen (PSA) as revealed in recent clinical trials, we tested the effects of lovastatin on the androgen signaling cascade in lymph node carcinoma of the prostate (LNCaP) prostate cancer cells. METHODS: Effects of lovastatin alone or in combination with a small interference RNA to inhibit AR expression on cell proliferation and induction of apoptosis were assessed by [(3)H] thymidine incorporation and caspase-3 activity assay. PSA levels were measured in the cell culture supernatant by immunoassay. In addition, expression and activity of AR and Akt/protein kinase B (Akt) were determined by Western blotting and real-time polymerase chain reaction as well as by luciferase reporter gene assay. RESULTS: Our results show that lovastatin significantly reduces AR expression and activity, resulting in decreased PSA levels. These effects were associated with inhibition of cell proliferation and induction of apoptosis. In addition, we observed that the Akt signaling pathway plays a pivotal role in lovastatin-mediated regulation of AR signaling. CONCLUSIONS: Our data suggest that the regular use of statins may have beneficial effects in statin users by preventing prostate cancer growth through inhibition of androgen activation and expression, resulting in diminished PSA levels.
OBJECTIVES: To investigate why statin users display a noticeable decline in prostate specific antigen (PSA) as revealed in recent clinical trials, we tested the effects of lovastatin on the androgen signaling cascade in lymph node carcinoma of the prostate (LNCaP) prostate cancer cells. METHODS: Effects of lovastatin alone or in combination with a small interference RNA to inhibit AR expression on cell proliferation and induction of apoptosis were assessed by [(3)H] thymidine incorporation and caspase-3 activity assay. PSA levels were measured in the cell culture supernatant by immunoassay. In addition, expression and activity of AR and Akt/protein kinase B (Akt) were determined by Western blotting and real-time polymerase chain reaction as well as by luciferase reporter gene assay. RESULTS: Our results show that lovastatin significantly reduces AR expression and activity, resulting in decreased PSA levels. These effects were associated with inhibition of cell proliferation and induction of apoptosis. In addition, we observed that the Akt signaling pathway plays a pivotal role in lovastatin-mediated regulation of AR signaling. CONCLUSIONS: Our data suggest that the regular use of statins may have beneficial effects in statin users by preventing prostate cancer growth through inhibition of androgen activation and expression, resulting in diminished PSA levels.
Authors: Sean Harrison; Kate Tilling; Emma L Turner; J Athene Lane; Andrew Simpkin; Michael Davis; Jenny Donovan; Freddie C Hamdy; David E Neal; Richard M Martin Journal: Cancer Causes Control Date: 2016-11-09 Impact factor: 2.506
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Authors: Abdulmajeed Aydh; Reza Sari Motlagh; Mishari Alshyarba; Keiichiro Mori; Satoshi Katayama; Nico Grossmann; Pawel Rajwa; Hadi Mostafai; Ekaterina Laukhtina; Benjamin Pradere; Fahad Quhal; Frederik König; Peter Nyirady; Pierre I Karakiewicz; Martin Haydter; Shahrokh F Shariat Journal: Cent European J Urol Date: 2021-12-06