Perillaldehyde is a new ferroptosis inducer with a relevant clinical potential for acute myeloid leukemia therapy

Catanzaro, Elena; Turrini, Eleonora; Kerre, Tessa; Sioen, Simon; Baeyens, Ans; Guerrini, Alessandra; Bellau, Mohamed Lamin Abdi; Sacchetti, Gianni; Paganetto, Guglielmo; Krysko, Dmitri V.; Fimognari, Carmela

doi:10.1016/j.biopha.2022.113662

Cited by 13 publications

(3 citation statements)

References 52 publications

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“…Hydnocarpin D is another flavonoid demonstrated to induce apoptosis and ferroptosis through autophagy in ALL cells [ 196 ]. Perillaldehyde, the main component of Ammodaucus leucotrichus , downregulates GSH and GPX4 to induce ferroptosis in HL-60 cells and primary AML cells [ 197 ]. Glycyrrhetinic acid is a bioactive compound of licorice, and its nanoparticles have been demonstrated to induce ferroptosis in AML cells through GPX4 downregulation [ 198 ].…”

Section: Ferroptosis In Leukemiamentioning

confidence: 99%

Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia

Akiyama

Carter

Andreeff

et al. 2023

Cells

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Ferroptosis is a mode of cell death regulated by iron-dependent lipid peroxidation. Growing evidence suggests ferroptosis induction as a novel anti-cancer modality that could potentially overcome therapy resistance in cancers. The molecular mechanisms involved in the regulation of ferroptosis are complex and highly dependent on context. Therefore, a comprehensive understanding of its execution and protection machinery in each tumor type is necessary for the implementation of this unique cell death mode to target individual cancers. Since most of the current evidence for ferroptosis regulation mechanisms is based on solid cancer studies, the knowledge of ferroptosis with regard to leukemia is largely lacking. In this review, we summarize the current understanding of ferroptosis-regulating mechanisms with respect to the metabolism of phospholipids and iron as well as major anti-oxidative pathways that protect cells from ferroptosis. We also highlight the diverse impact of p53, a master regulator of cell death and cellular metabolic processes, on the regulation of ferroptosis. Lastly, we discuss recent ferroptosis studies in leukemia and provide a future perspective for the development of promising anti-leukemia therapies implementing ferroptosis induction.

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Section: Ferroptosis In Leukemiamentioning

confidence: 99%

Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia

Akiyama

Carter

Andreeff

et al. 2023

Cells

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“…These include investigating the effects of combining erastin with chemotherapy drugs [98] or the ferroptotic effects of other agents, such as the antimalarial drug dihydroartemisinin [99,100], a novel all-trans retinoic acid derivative [101] and the cir-cRNAs circKDM4C, which upregulates ferroptosis [102] and circZBTB46 which prevents ferroptosis [103]. Natural derivatives with ferroptosis-inducing potential in AML have also been identified including a pollen flavonoid extract, typhaneoside [104], a monoterpenoid plant extract, perillaldehyde [105], or the diterpenoid epoxide plant extract, triptolide, which induces ferroptosis to sensitise AML and CML cells to doxorubicin [97]. Inhibitors of aldehyde dehydrogenase 3a2 and GPX4 have also been shown to synergise and induce cell death via ferroptosis in AML cells, both in vitro and in vivo [106].…”

Section: Acute Myeloid Leukaemiamentioning

confidence: 99%

Ferroptosis in Haematological Malignancies and Associated Therapeutic Nanotechnologies

Mynott

Ali

Best

et al. 2023

IJMS

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Haematological malignancies are heterogeneous groups of cancers of the bone marrow, blood or lymph nodes, and while therapeutic advances have greatly improved the lifespan and quality of life of those afflicted, many of these cancers remain incurable. The iron-dependent, lipid oxidation-mediated form of cell death, ferroptosis, has emerged as a promising pathway to induce cancer cell death, particularly in those malignancies that are resistant to traditional apoptosis-inducing therapies. Although promising findings have been published in several solid and haematological malignancies, the major drawbacks of ferroptosis-inducing therapies are efficient drug delivery and toxicities to healthy tissue. The development of tumour-targeting and precision medicines, particularly when combined with nanotechnologies, holds potential as a way in which to overcome these obstacles and progress ferroptosis-inducing therapies into the clinic. Here, we review the current state-of-play of ferroptosis in haematological malignancies as well as encouraging discoveries in the field of ferroptosis nanotechnologies. While the research into ferroptosis nanotechnologies in haematological malignancies is limited, its pre-clinical success in solid tumours suggests this is a very feasible therapeutic approach to treat blood cancers such as multiple myeloma, lymphoma and leukaemia.

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“…Perillaldehyde and limonene are commercially used as flavors and preservatives in foods and perfumes [30,31]. Moreover, some studies reported antidepressant effects in stress-induced depression-like model mice and anticancer effects for perillaldehyde [32][33][34] and Ras-independent anticancer effects on PANC-1 pancreas carcinoma cells for limonene [35].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Investigation of the Anticancer Properties of Ammodaucus Leucotrichus Coss. & Dur.

et al. 2022

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Little is known about the pharmacological activity of Ammodaucus leucotrichus Coss. & Dur., a small annual species that grows in the Saharan and sub-Saharan countries. In the present study, we investigated whether the standardized ethanolic extract of A. leucotrichus fruits and R-perillaldehyde, a monoterpenoid isolated from A. leucotrichus fruits, are able to affect different processes involved in different phases of cancer development. In particular, we explored their genoprotective, proapoptotic, antiproliferative, and cytodifferentiating potential on different human cell models. We analyzed the genoprotective and proapoptotic activity on human lymphoblast cells (TK6) using the micronucleus test, and the cytodifferentiation effects on human promyelocytic cells (HL60) through the evaluation of different markers of differentiation forward granulocytes or monocytes. The results showed that the extract and perillaldehyde were able to induce apoptosis and protect from clastogen-induced DNA damage. To our best knowledge, this is the first report on the ability of A. leucotrichus and perillaldehyde to induce apoptosis and protect DNA from the toxicity of different compounds. Data reported in this work are the starting point for their pharmacological use. Going forward, efforts to determine their effects on other events associated with cancer development, such as angiogenesis and metastasization, will provide important information and improve our understanding of their potential in cancer therapy.

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Perillaldehyde is a new ferroptosis inducer with a relevant clinical potential for acute myeloid leukemia therapy

Cited by 13 publications

References 52 publications

Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia

Molecular Mechanisms of Ferroptosis and Updates of Ferroptosis Studies in Cancers and Leukemia

Ferroptosis in Haematological Malignancies and Associated Therapeutic Nanotechnologies

In Vitro Investigation of the Anticancer Properties of Ammodaucus Leucotrichus Coss. & Dur.

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