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. 2024 Nov;103(11):4511-4524.
doi: 10.1007/s00277-024-06003-4. Epub 2024 Sep 12.

Licochalcone A decreases cancer cell proliferation and enhances ferroptosis in acute myeloid leukemia through suppressing the IGF2BP3/MDM2 cascade

Pingping Han  1 , Suhua Wei  2 , Huaiyu Wang  2 , Yun Cai  3
Affiliations

Licochalcone A decreases cancer cell proliferation and enhances ferroptosis in acute myeloid leukemia through suppressing the IGF2BP3/MDM2 cascade

Pingping Han et al. Ann Hematol. 2024 Nov.

Abstract

Licochalcone A (Lico A), a naturally bioactive flavonoid, has shown antitumor activity in several types of cancers. However, few studies have focused on its effect on acute myeloid leukemia (AML). Cell viability and colony formation potential were detected by CCK-8 assay and colony formation assay, respectively. Cell cycle distribution and apoptosis were assessed by flow cytometry. Ferroptosis was assessed by measuring reactive oxygen species (ROS), lipid ROS, malondialdehyde (MDA), and glutathione (GSH). Protein expression levels were determined by immunoblotting and immunohistochemistry (IHC), and mRNA expression was detected by real-time qPCR. The m6A modification of MDM2 mRNA was verified by methylated RNA immunoprecipitation (MeRIP) assay, and the interaction of IGF2BP3 and MDM2 mRNA was analyzed by RIP assay. Actinomycin D was used to evaluate mRNA stability. The efficacy of Lico A in vivo was examined by a murine xenograft model. Lico A suppressed cell proliferation and induced ferroptosis in MOLM-13 and U-937 in vitro, and slowed the growth of xenograft tumors in vivo. IGF2BP3 was highly expressed in human AML specimens and cells, and Lico A suppressed IGF2BP3 expression in AML cells. Lico A exerted the anti-proliferative and pro-ferroptosis effects by downregulating IGF2BP3. Moreover, IGF2BP3 enhanced the stability and expression of MDM2 mRNA through an m6A-dependent manner. Downregulation of IGF2BP3 impeded AML cell proliferation and enhanced ferroptosis via repressing MDM2. Furthermore, Lico A could affect the MDM2/p53 pathway by downregulating IGF2BP3 expression. Lico A exerts the anti-proliferative and pro-ferroptosis activity in AML cells by affecting the IGF2BP3/MDM2/p53 pathway, providing new evidence for Lico A as a promising agent for the treatment of AML.

Keywords: Acute myeloid leukemia; IGF2BP3; Licochalcone A; MDM2/p53 pathway; m6A modification.

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References

    1. Saultz JN, Garzon R (2016) Acute myeloid leukemia: a concise review. J Clin Med 5(3):33. https://doi.org/10.3390/jcm5030033 - DOI - PubMed - PMC
    1. Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM (2019) Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev 36:70–87. https://doi.org/10.1016/j.blre.2019.04.005 - DOI - PubMed
    1. Shimony S, Stahl M, Stone RM (2023) Acute myeloid leukemia: 2023 update on diagnosis, risk-stratification, and management. Am J Hematol 98(3):502–526. https://doi.org/10.1002/ajh.26822 - DOI - PubMed
    1. Fleischmann M, Schnetzke U, Hochhaus A, Scholl S (2021) Management of Acute myeloid leukemia: current treatment options and future perspectives. Cancers 13(22):5722. https://doi.org/10.3390/cancers13225722 - DOI - PubMed - PMC
    1. Li MT, Xie L, Jiang HM, Huang Q, Tong RS, Li X, Xie X, Liu HM (2022) Role of Licochalcone A in potential pharmacological therapy: a review. Front Pharmacol 13:878776. https://doi.org/10.3389/fphar.2022.878776 - DOI - PubMed - PMC

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