2. Academic Validation
  3. Licochalcone A induces mitochondria-dependent apoptosis and interacts with venetoclax in acute myeloid leukemia

Licochalcone A induces mitochondria-dependent apoptosis and interacts with venetoclax in acute myeloid leukemia

  • Eur J Pharmacol. 2024 Feb 11:968:176418. doi: 10.1016/j.ejphar.2024.176418.
Youhong Li 1,  Mengting Zhao 2,  Ye Lin 2,  Xia Jiang 1,  Lili Jin 1,  Peipei Ye 3,  Ying Lu 3,  Renzhi Pei 4,  Lei Jiang 5
Affiliations

Affiliations

  • 1 Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, China; Department of Pathology and Pathogenic Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, China; Institute of Hematology, Ningbo University, Ningbo, China.
  • 2 Department of Pathology and Pathogenic Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, China.
  • 3 Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, China; Institute of Hematology, Ningbo University, Ningbo, China.
  • 4 Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, China; Institute of Hematology, Ningbo University, Ningbo, China. Electronic address: [email protected].
  • 5 Department of Hematology, The Affiliated People's Hospital of Ningbo University, Ningbo, China; Department of Pathology and Pathogenic Biology, and Zhejiang Key Laboratory of Pathophysiology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, China. Electronic address: [email protected].
PMID: 38350590 DOI: 10.1016/j.ejphar.2024.176418
Abstract

The management of patients with acute myeloid leukemia (AML) remains a challenge because of the complexity and heterogeneity of this malignancy. Despite the recent approval of several novel targeted drugs, resistance seems inevitable, and clinical outcomes are still suboptimal. Increasing evidence supports the use of natural Plants as an important source of anti-leukemic therapeutics. Licochalcone A (LCA) is an active flavonoid isolated from the roots of licorice, Glycyrrhiza uralensis Fisch., possessing extensive anti-tumor activities. However, its effects on AML and the underlying mechanisms remain unknown. Here, we showed that LCA decreased the viability of established human AML cell lines in a dose- and time-dependent manner. LCA significantly induced mitochondrial apoptotic cell death, accompanied by the downregulation of Mcl-1, upregulation of Bim, truncation of BID, and cleavage of PARP. A prominent decline in the phosphorylation of multiple critical molecules, including Akt, glycogen synthase kinase-3β (GSK3β), ERK, and P38 was observed upon LCA treatment, indicating PI3K and MAPK signals were suppressed. Both transcription and translation of c-Myc were also inhibited by LCA. In addition, LCA enhanced the cytotoxicity of the Bcl-2 Inhibitor venetoclax. Furthermore, the anti-survival and pro-apoptotic effects were confirmed in primary blasts from 10 patients with de novo AML. Thus, our results expand the applications of LCA, which can be regarded as a valuable agent in treating AML.

Keywords

Acute myeloid leukemia; Apoptosis; Licochalcone A; Venetoclax; c-Myc.

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