α-Hexylcinnamaldehyde Synergistically Increases Doxorubicin Cytotoxicity Towards Human Cancer Cell Lines

  • Anticancer Res. 2016 Jul;36(7):3347-51.
Silvia DI Giacomo  1 ,  Antonella DI Sotto  2 ,  Mahmoud Zaki El-Readi  3 ,  Gabriela Mazzanti  1 ,  Michael Wink  3
Affiliations
  • 1. Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Rome, Italy.
  • 2. Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Rome, Italy [email protected].
  • 3. Institute of Pharmacy and Molecular Biotechnology, Ruprecht Karls University, Heidelberg, Germany.
PMID: 27354593
Abstract

Aim: α-Hexylcinnamaldehyde (HCA), a compound derived from cinnamaldehyde, was evaluated for its potential chemosensitizing properties.

Materials and methods: The cytotoxicity of HCA was tested against Caco-2, CCRF/CEM and CEM/ADR5000 human Cancer cells. Furthermore, its ability to increase doxorubicin cytotoxicity was evaluated in combination assays. Rhodamine123 efflux assay was carried out in order to highlight the possible interference of HCA with functionality of ATP-binding cassette (ABC)-transporters.

Results: In spite of a low cytotoxicity, HCA increased the antiproliferative effect of doxorubicin in all the cell lines tested, being particularly effective in CCRF/CEM. The compound also reduced the rhodamine123 efflux in Caco-2 and CEM/ADR5000 cells, suggesting a possible interference with ABC transporter functionality.

Conclusion: Considering that the greatest synergism between HCA and DOX was found against CCRF/CEM cells (lacking ABC pumps), it seems likely that non-specific mechanisms, including the alteration of membrane permeability, could be involved in the chemosensitizing effect of HCA.

Keywords
ABC-transporters; Cinnamaldehyde; MDR reversal agent; chemosensitizer; naturally-derived compound.
Products