PT  - JOURNAL ARTICLE
AU  - WALTERS, COLE
AU  - REED, MAVERICK
AU  - BARTHOLOMEW, SAMANTHA
AU  - BOMMAREDDY, AJAY
TI  - Autophagy Induction by α-Santalol in Human Prostate Cancer Cells
AID  - 10.21873/anticanres.14876
DP  - 2021 Mar 01
TA  - Anticancer Research
PG  - 1197--1202
VI  - 41
IP  - 3
4099  - http://ar.iiarjournals.org/content/41/3/1197.short
4100  - http://ar.iiarjournals.org/content/41/3/1197.full
SO  - Anticancer Res2021 Mar 01; 41
AB  - Background/Aim: Previous studies have shown that the sandalwood oil constituent α-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 α-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 α-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 α-santalol with/without 3-methyl adenine on the cell viability of prostate cancer cells. Acidic vesicular organelles induced by α-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 α-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 AKT and mTOR, which are critical regulators of autophagic response. In addition, pre-treatment of PC-3 cells with specific inhibitor of autophagy (3-methyladenine) and co-treatment with α-santalol attenuated the expression of LC3-II and phospho-AKT, and significantly reduced the cell viability. Conclusion: The present study indicates that α-santalol induces autophagy by targeting the AKT–mTOR pathway in prostate cancer cells, which may serve as a protective mechanism.