Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 154, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113662
Keywords
Ammodaucus leucotrichus; R-perillaldehyde; Ferroptosis; ATP; Acute myeloid leukemia
Funding
- University of Ferrara
- FFABR MIUR
- FWO-Flanders [G043219N, FWO G016221]
- Ghent University BOF [01/O3618, BOF/IOP/2022/033]
- FWO [40007488]
- F.R.S.-FNRS
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This study investigates the potential of the monoterpene compound perillaldehyde to induce ferroptosis in leukemia cells. Perillaldehyde induces lipid peroxidation, decreases the expression of a specific protein, and reduces intracellular glutathione. Additionally, it stimulates the secretion of ATP.
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.
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