Autophagy Induction by α-Santalol in Human Prostate Cancer Cells.

Publication/Presentation Date

3-1-2021

Abstract

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.

Volume

41

Issue

3

First Page

1197

Last Page

1202

ISSN

1791-7530

Disciplines

Medicine and Health Sciences | Pharmacy and Pharmaceutical Sciences

PubMedID

33788710

Department(s)

Department of Pharmacy

Document Type

Article

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