Phosphodiesterase Type-5 Inhibitor Tadalafil Modulates Steroid Hormones Signaling in a Prostate Cancer Cell Line.
Level 5 - mechanism / opinion, no new human data
Bench research / in vitro cell culture study
PubMed 33451122 · doi:10.3390/ijms22020754
What was done
Researchers treated androgen-sensitive human prostate cancer cells (LnCAP) with or without the phosphodiesterase type-5 inhibitor tadalafil (10^-6 M) and the antiandrogen bicalutamide (10^-4 M). They measured cell proliferation as well as the mRNA and protein expression and transcriptional activity of the androgen receptor (AR), aromatase (Cyp19a1), and estrogen receptor-beta (ERβ).
What was found
Tadalafil significantly increased early AR nuclear translocation after 15 minutes (p < 0.05), and increased AR transcriptional activity (p < 0.05) and protein expression (p < 0.05) after 24 hours. At 24 hours, tadalafil upregulated Cyp19a1 (p < 0.05) and ERβ mRNA (p < 0.005), leading to increased protein expression of both targets at 48 hours (p < 0.05). Tadalafil counteracted the bicalutamide-induced stimulation of Cyp19a1 (p < 0.05) without altering bicalutamide's effect on AR protein expression. The abstract states that tadalafil potentiated the antiproliferative effect of bicalutamide, but specific numerical values, effect sizes, or proliferation percentages were not reported.
Why it matters
This study provides in vitro mechanistic evidence that tadalafil can alter steroid hormone receptor signaling and aromatase expression in prostate cancer cells, suggesting potential interactions with androgen deprivation agents like bicalutamide.
Limits
The study is restricted to an in vitro model using a single cell line (LnCAP), so findings cannot be directly extrapolated to in vivo physiology or clinical outcomes. Numerical details regarding the degree of proliferation inhibition, sample replicates, and exact effect magnitudes are omitted from the abstract.
Cited by
- partial Tadalafil upregulates either the sensitivity or the number of androgen receptors, enhancing the body's response to circulating testosterone.