Perillaldehyde is a new ferroptosis inducer with a relevant clinical potential for acute myeloid leukemia therapy
Autor: | Elena Catanzaro, Eleonora Turrini, Tessa Kerre, Simon Sioen, Ans Baeyens, Alessandra Guerrini, Mohamed Lamin Abdi Bellau, Gianni Sacchetti, Guglielmo Paganetto, Dmitri V. Krysko, Carmela Fimognari |
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Přispěvatelé: | Catanzaro E., Turrini E., Kerre T., Sioen S., Baeyens A., Guerrini A., Bellau M.L.A., Sacchetti G., Paganetto G., Krysko D.V., Fimognari C. |
Jazyk: | angličtina |
Rok vydání: | 2022 |
Předmět: |
Pharmacology
DAMPs Ammodaucus leucotrichus R-perillaldehyde Ferroptosis ATP Acute myeloid leukemia Acute myeloid leukemia Leukemia Cell Death Socio-culturale Ambientale Biology and Life Sciences General Medicine Ammodaucus leucotrichus ATP Ferroptosis R-perillaldehyde Medicine and Health Sciences LS7_3 Immunogenic cell death |
Zdroj: | BIOMEDICINE & PHARMACOTHERAPY |
ISSN: | 0753-3322 1950-6007 |
Popis: | Ferroptosis induction is an emerging strategy to treat cancer and contrast the tricky issue of chemoresistance, which can arise towards apoptosis. This work elucidates the anticancer mechanisms evoked by perillaldehyde, a monoterpenoid isolated from Ammodaucus leucotrichus Coss. & Dur. We investigated and characterized its antileukemic potential in vitro, disclosing its ability to trigger ferroptosis. Specifically, perillaldehyde induced lipid peroxidation, decreased glutathione peroxidase 4 protein expression, and depleted intracellular glutathione on HL-60 promyelocytic leukemia cells. Besides, it stimulated the active secretion of ATP, one of the most crucial events in the induction of efficient anticancer response, prompting further studies to disclose its possible nature as an immunogenic cell death inducer. To preliminarily assess the clinical relevance of perillaldehyde, we tested its ability to induce cell death on patient-derived acute myeloid leukemia biopsies, recording a similar mechanism of action and potency compared to HL-60 cells. To round the study off, we tested its selectivity towards tumor cells and disclosed lower toxicity on normal cells compared to both HL-60 and acute myeloid leukemia biopsies. Altogether, these data depict a favorable risk-benefit profile for perillaldehyde and reveal its peculiar antileukemic potential, which qualifies this natural product to proceed further through the drug development pipeline. |
Databáze: | OpenAIRE |
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