tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a promising anticancer agent, as it selectively induces apoptosis in transformed cells without altering the cellular machinery of healthy cells. Unfortunately, the presence of TRAIL resistance mechanisms in a variety of cancer types represents a major hurdle, thus limiting the use of TRAIL as a single agent. accumulating studies have shown that TRAIL-mediated apoptosis can be facilitated in resistant tumors by combined treatment with antitumor agents, ranging from synthetic molecules to natural products. among the latter, flavonoids, the most prevalent polyphenols in plants, have shown remarkable competence in improving TRAIL-driven apoptosis in resistant cell lines as well as tumor-bearing mice with minimal side effects. here, we summarize the molecular mechanisms, such as the upregulation of death receptor (DR)4 and DR5 and downregulation of key anti-apoptotic proteins [e.g., cellular FLICE-inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), survivin], underlying the TRAIL-sensitizing properties of different classes of flavonoids (e.g., flavones, flavonols, isoflavones, chalcones, prenylflavonoids). Finally, we discuss limitations, mainly related to bioavailability issues, and future perspectives regarding the clinical use of flavonoids as adjuvant agents in TRAIL-based therapies.

Luiz-Ferreira, A., Pacifico, T., Cardoso Cruz, A., Laudisi, F., Monteleone, G., Stolfi, C. (2023). TRAIL-Sensitizing Effects of Flavonoids in Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(23) [10.3390/ijms242316596].

TRAIL-Sensitizing Effects of Flavonoids in Cancer

Teresa Pacifico;Giovanni Monteleone;Carmine Stolfi
2023-01-01

Abstract

tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents a promising anticancer agent, as it selectively induces apoptosis in transformed cells without altering the cellular machinery of healthy cells. Unfortunately, the presence of TRAIL resistance mechanisms in a variety of cancer types represents a major hurdle, thus limiting the use of TRAIL as a single agent. accumulating studies have shown that TRAIL-mediated apoptosis can be facilitated in resistant tumors by combined treatment with antitumor agents, ranging from synthetic molecules to natural products. among the latter, flavonoids, the most prevalent polyphenols in plants, have shown remarkable competence in improving TRAIL-driven apoptosis in resistant cell lines as well as tumor-bearing mice with minimal side effects. here, we summarize the molecular mechanisms, such as the upregulation of death receptor (DR)4 and DR5 and downregulation of key anti-apoptotic proteins [e.g., cellular FLICE-inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), survivin], underlying the TRAIL-sensitizing properties of different classes of flavonoids (e.g., flavones, flavonols, isoflavones, chalcones, prenylflavonoids). Finally, we discuss limitations, mainly related to bioavailability issues, and future perspectives regarding the clinical use of flavonoids as adjuvant agents in TRAIL-based therapies.
2023
Pubblicato
Rilevanza internazionale
Review
Esperti anonimi
Settore MED/12
Settore MED/50
English
DR4
DR5
apoptosis
c-FLIP
caspase-8
medicinal plants
natural products
polyphenols
survivin
tumor necrosis factor related apoptosis-inducing ligand
Luiz-Ferreira, A., Pacifico, T., Cardoso Cruz, A., Laudisi, F., Monteleone, G., Stolfi, C. (2023). TRAIL-Sensitizing Effects of Flavonoids in Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24(23) [10.3390/ijms242316596].
Luiz-Ferreira, A; Pacifico, T; Cardoso Cruz, A; Laudisi, F; Monteleone, G; Stolfi, C
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/351624
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