RT Journal Article SR Electronic T1 α-Hexylcinnamaldehyde Synergistically Increases Doxorubicin Cytotoxicity Towards Human Cancer Cell Lines JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3347 OP 3351 VO 36 IS 7 A1 SILVIA DI GIACOMO A1 ANTONELLA DI SOTTO A1 MAHMOUD ZAKI EL-READI A1 GABRIELA MAZZANTI A1 MICHAEL WINK YR 2016 UL http://ar.iiarjournals.org/content/36/7/3347.abstract AB 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.