LCC03 is a salicylanilide derivative and autophagy inducer, dose-dependently suppresses proliferation and retarded cell-cycle progression in CRPC cells (IC50, 0.69 to 4.8 uM).The classical autophagy features, including autophagosome formation and LC3-II conversion, were dramatically shown in LCC03-treated CRPC cells, which was associated with the suppressed AKT/mTOR signaling pathways, a major negative regulator of autophagy.LCC03 also showed an expanded morphology of the endoplasmic reticulum (ER), increased expression of the ER stress markers GRP78 and PERK, and eIF2α phosphorylation.The PERK-eIF2α pathway contributed to the LCC03-induced autophagy.LCC03 suppressed the growth of CRPC xenografts in mouse bone without systemic toxicity in tumor-bearing mice.
