Autophagy Induction By Alpha-Santalol In Human Prostate Cancer Cells

Background/Aim: Previous studies have shown that the sandalwood oil constituent ?-santalol inhibits growth of cultured human prostate cancer cells in vitro and PC-3 prostate cancer xenografts. Along with the studies from our laboratory, it is well established that ?-santalol targets the phosphatidylinositol-4,5-bisphosphate 3-kinase?AKT serine/ threonine kinase 1 (AKT) pathway to induce apoptosis but its growth-suppressive effects have not been fully elucidated. The current study was undertaken to investigate the role of autophagy in ?-santalol-induced prostate cancer cell death. Materials and Methods: Cell lines LNCaP and PC-3 were maintained in an atmosphere of 95% air and 5% CO2 at 37?C. Trypan blue dye exclusion assay was employed to assess the effects of ?-santalol with/without 3-methyl adenine on the cell viability of prostate cancer cells. Acidic vesicular organelles induced by ?-santalol treatment were detected by staining with acridine orange. Immunofluorescence and immunoblotting were performed to analyze expression of proteins involved in the AKT-mammalian target of rapamycin (mTOR) pathway. Results: LNCaP and PC-3 cells upon treatment with ?-santalol resulted in characteristic features analogous to autophagic response, including formation of acidic vesicular organelles, recruitment and cleavage of microtubule-associated protein 1 light chain 3 (LC3) to autophagosomes. Alpha-santalol treatment further suppressed phosphorylation of activated ??? and mTOR, which are critical regulators of autophagic response. In addition, pretreatment of PC-3 cells with specific inhibitor of autophagy