Drug resistance is the ability of cancer cells to gain resistance to both conventional and novel chemotherapy agents, and remains a major problem in cancer therapy. Resistance mechanisms are multifactorial and involve more strictly pharmacological factors, such as P-glycoprotein (P-gp) and biological factors such as inhibitor of apoptosis proteins (IAPs) and the nuclear factor-kappa B (NF-kB) pathway. Possible therapeutic strategies for the treatment of acute myeloid leukemia (AML) have increased in recent years; however, drug resistance remains a problem for most pa-tients. Phytol and heptacosane are the major compounds of Euphorbia intisy essential oil (EO) which were demonstrated to inhibit P-gp in a multidrug resistant in vitro model of AML. This study investigated the mechanism by which phytol and heptacosane improve P-gp-mediated drug transport. Phytol suppresses the P-gp expression via NF-kB inhibition and does not seem to act on the efflux system. Heptacosane acts as a substrate and potent P-gp inhibitor, demonstrating the ability to retain the substrate doxorubicin inside the cell and enhancing its cytotoxic effects. Our results suggest that these compounds act as non-toxic modulators of P-gp through different mechanisms and are able to revert P-gp-mediated drug resistance in tumor cells.

Manuela Labbozzetta, Paola Poma, Marco Tutone, James A. McCubrey, Maurizio Sajeva, Monica Notarbartolo (2022). Phytol and Heptacosane Are Possible Tools to Overcome Multidrug Resistance in an In Vitro Model of Acute Myeloid Leukemia. PHARMACEUTICALS, 15(3), 1-22 [10.3390/ ph15030356].

Phytol and Heptacosane Are Possible Tools to Overcome Multidrug Resistance in an In Vitro Model of Acute Myeloid Leukemia

Manuela Labbozzetta
Primo
;
Paola Poma
Secondo
;
Marco Tutone;Maurizio Sajeva;Monica Notarbartolo
Ultimo
2022-03-15

Abstract

Drug resistance is the ability of cancer cells to gain resistance to both conventional and novel chemotherapy agents, and remains a major problem in cancer therapy. Resistance mechanisms are multifactorial and involve more strictly pharmacological factors, such as P-glycoprotein (P-gp) and biological factors such as inhibitor of apoptosis proteins (IAPs) and the nuclear factor-kappa B (NF-kB) pathway. Possible therapeutic strategies for the treatment of acute myeloid leukemia (AML) have increased in recent years; however, drug resistance remains a problem for most pa-tients. Phytol and heptacosane are the major compounds of Euphorbia intisy essential oil (EO) which were demonstrated to inhibit P-gp in a multidrug resistant in vitro model of AML. This study investigated the mechanism by which phytol and heptacosane improve P-gp-mediated drug transport. Phytol suppresses the P-gp expression via NF-kB inhibition and does not seem to act on the efflux system. Heptacosane acts as a substrate and potent P-gp inhibitor, demonstrating the ability to retain the substrate doxorubicin inside the cell and enhancing its cytotoxic effects. Our results suggest that these compounds act as non-toxic modulators of P-gp through different mechanisms and are able to revert P-gp-mediated drug resistance in tumor cells.
Settore BIO/14 - Farmacologia
Settore CHIM/08 - Chimica Farmaceutica
https://www.mdpi.com/1424-8247/15/3/356
Manuela Labbozzetta, Paola Poma, Marco Tutone, James A. McCubrey, Maurizio Sajeva, Monica Notarbartolo (2022). Phytol and Heptacosane Are Possible Tools to Overcome Multidrug Resistance in an In Vitro Model of Acute Myeloid Leukemia. PHARMACEUTICALS, 15(3), 1-22 [10.3390/ ph15030356].
File in questo prodotto:
File Dimensione Formato  
2022_pharmaceuticals_Heptacosane.pdf

accesso aperto

Descrizione: Articolo con materiale supplementare
Tipologia: Versione Editoriale
Dimensione 4.5 MB
Formato Adobe PDF
4.5 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/546192
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 4
social impact