2. Academic Validation
  3. Autophagy Induction by α-Santalol in Human Prostate Cancer Cells

Autophagy Induction by α-Santalol in Human Prostate Cancer Cells

  • Anticancer Res. 2021 Mar;41(3):1197-1202. doi: 10.21873/anticanres.14876.
Cole Walters 1,  Maverick Reed 1,  Samantha Bartholomew 1,  Ajay Bommareddy 2
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A.
  • 2 Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, PA, U.S.A. ajay.bommareddy@wilkes.edu.
PMID: 33788710 DOI: 10.21873/anticanres.14876
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.

Keywords

Prostate cancer; alpha-santalol; autophagosomes; autophagy.

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