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Synthesis and evaluation of apoptotic induction of human cancer cells by ester derivatives of thujone

  • Emily Castner
  • Matthew Dickson
  • Anna Mykytyn
  • Navindra P. Seeram
  • Geneive E. HenryEmail author
  • Pavithra VivekanandEmail author
Original Research
  • 17 Downloads

Abstract

Thujone (1), thujol (2), and aromatic thujol esters (3–9) were evaluated for their ability to induce cell death in human cervical (HeLa), melanoma (A375), and colon (HCT-116) cancer cell lines, using etoposide as a positive control. The compounds showed dose-dependent activity at concentrations ranging from 50–400 μg/mL. Etoposide exhibited an IC50 value of 116 μg/mL in HeLa cells, and α-thujone, α/β-thujone (7:1), and thujol showed comparable activity with IC50 values of 191, 198, and 136 μg/mL, respectively. All seven ester derivatives were cytotoxic to HeLa and HCT-116 cells, while a subset was cytotoxic to A375 cells. In HeLa cells, t-cinnamate (4), t-isonicotinate (5), t-nicotinate (6), and t-furoate (8) were more potent than either α-thujone or α/β-thujone. Similarly, t-furoate (8) was more potent than thujone in A375 cells, and t-isonicotinate (5) and t-nicotinate (6) were more potent against HCT-116 cells. Based on cell morphology, PARP cleavage and an increase in the caspase-3/7 levels, the esters exert their cytotoxic effects by induction of apoptosis.

Keywords

Thujone Thujol esters HeLa cells HCT-116 cells A375 cells Anticancer Cell death induction Apoptosis 

Notes

Acknowledgements

We are grateful to Susquehanna University for financial support of this project. The Waters SYNAPT G2-S QTOFMS system used for HRMS data was obtained by a grant (# P20GM103430) from National Center for Research Resources (NCRR). The JEOL ECZ 400S NMR spectrometer was acquired by a grant to Susquehanna University from the National Science Foundation (NSF:MRI CHE 1625340). The Thermo Scientific Nicolet iS50 FT-IR spectrometer was funded by the Sherman Fairchild Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of ChemistrySusquehanna UniversitySelinsgroveUSA
  2. 2.Department of BiologySusquehanna UniversitySelinsgroveUSA
  3. 3.Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of PharmacyUniversity of Rhode IslandKingstonUSA

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