Silvia DI Giacomo1, Antonella DI Sotto2, Mahmoud Zaki El-Readi3, Gabriela Mazzanti1, Michael Wink3. 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 antonella.disotto@uniroma1.it. 3. Institute of Pharmacy and Molecular Biotechnology, Ruprecht Karls University, Heidelberg, Germany.
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. Copyright
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 humancancer cells. Furthermore, its ability to increase doxorubicincytotoxicity 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. Copyright
Authors: Silvia Di Giacomo; Marco Gullì; Roberta Facchinetti; Marco Minacori; Romina Mancinelli; Ester Percaccio; Caterina Scuderi; Margherita Eufemi; Antonella Di Sotto Journal: Pharmaceutics Date: 2022-06-14 Impact factor: 6.525