title: α-Hexylcinnamaldehyde Synergistically Increases Doxorubicin Cytotoxicity Towards Human Cancer Cell Lines.
abstract: OBJECTIVE
  α-Hexylcinnamaldehyde (HCA), a compound derived from cinnamaldehyde, was evaluated for its potential chemosensitizing properties.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: DI Giacomo
authors.affiliation: Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Rome, Italy antonella.disotto@uniroma1.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: DI Sotto
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Ruprecht Karls University, Heidelberg, Germany.
authors.forename: Mahmoud Zaki
authors.initials: MZ
authors.lastname: El-Readi
authors.affiliation: Department of Physiology and Pharmacology V. Erspamer, Sapienza University of Rome, Rome, Italy.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Mazzanti
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Ruprecht Karls University, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wink
mesh_terms: D000171:Acrolein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans
chemical_list: C551429:alpha-hexylcinnamaldehyde; D000171:Acrolein; D004317:Doxorubicin
keywords: ABC-transporters; Cinnamaldehyde; MDR reversal agent; chemosensitizer; naturally-derived compound