PT - JOURNAL ARTICLE AU - SILVIA DI GIACOMO AU - ANTONELLA DI SOTTO AU - MAHMOUD ZAKI EL-READI AU - GABRIELA MAZZANTI AU - MICHAEL WINK TI - α-Hexylcinnamaldehyde Synergistically Increases Doxorubicin Cytotoxicity Towards Human Cancer Cell Lines DP - 2016 Jul 01 TA - Anticancer Research PG - 3347--3351 VI - 36 IP - 7 4099 - http://ar.iiarjournals.org/content/36/7/3347.short 4100 - http://ar.iiarjournals.org/content/36/7/3347.full SO - Anticancer Res2016 Jul 01; 36 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.