Using LN-CAP, DU-145, and PC-3 cell lines, effects of minocycline on microsomal RA metabolism and on cell growth were assessed in聽vitro.
Minocycline was identified to potently inhibit cell growth, at concentrations within the range of tissue levels readily reached under standard therapeutic conditions. In聽vitro inhibition experiments revealed inhibition of RA breakdown, yet only at comparably high concentrations of minocycline. Using all trans-RA, RA metabolism inhibitor liarozole, and different retinoid receptor antagonists, the putative RA-dependent effects of minocycline were further evaluated and confirmed to be independent of RA signaling.
Our findings add to the growing body of evidence for the many pleiotropic actions of minocycline. In view of the striking effects of minocycline on cell growth in PCA cell lines in聽vitro and its relatively safe side effect profile, the use of minocycline for targeting PCA should be timely clinically evaluated.