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Planta Med 2023; 89(13): 1204-1214
DOI: 10.1055/a-2114-0980
Biological and Pharmacological Activity
Original Papers

1-Methoxyerythrabyssin II Induces Autophagy in Leukemia Cells via PI3K/Akt/mTOR Pathways

Bo Fang
1   College of Pharmacy, Wenzhou Medical University, Wenzhou, China
2   Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju, Korea
,
Soeun Kim
2   Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju, Korea
,
Yebon Kim
2   Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju, Korea
,
Yinda Qiu
1   College of Pharmacy, Wenzhou Medical University, Wenzhou, China
2   Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju, Korea
,
Chang-Min Lee
3   Department of Veterinary Internal Medicine, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju, Korea
,
Yinshuang Lai
1   College of Pharmacy, Wenzhou Medical University, Wenzhou, China
,
Zhiguo Liu   *
1   College of Pharmacy, Wenzhou Medical University, Wenzhou, China
,
Kun Wang   *
1   College of Pharmacy, Wenzhou Medical University, Wenzhou, China
,
Namki Cho   *
2   Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju, Korea
› Author AffiliationsThis research was supported by a grant from the National Research Foundation (NRF) of Korea funded by the Korean government (MSIT) (grant number: NRF-2022R1C1C1009626). In addition, this work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) under grant number 2022R1F1A1 059 721.
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Abstract

Leukemia, despite currently being one of the most lethal cancers worldwide, still lacks a focused treatment. The purpose of the present investigation was to evaluate the pharmacological effect of 1-methoxyerythrabyssin II, a pterocarpan identified in the roots of Lespedeza bicolor, on leukemic cells and to explore its underlying mechanism using a network pharmacology strategy. 1-Methoxyerythrabyssin II showed an antiproliferative effect in a concentration-dependent manner and exhibited a higher potency in human acute leukemia T cells (Jurkat). The G1 phase arrest induced by 1-methoxyerythrabyssin II was confirmed using a cell cycle assay, and the downregulation of CDK2 and cyclin D1 was observed using an immunoblot assay. Moreover, 1-methoxyerythrabyssin II-treated cells exhibited higher expression levels of LC3B, Atg-7, and Beclin 1 in addition to an enhanced fluorescence intensity in monodansylcadaverine staining, indicating autophagy induction by 1-methoxyerythrabyssin II. Furthermore, network pharmacology and molecular docking analyses revealed that the PI3K/Akt/mTOR pathway is a potential target of 1-methoxyerythrabyssin II in leukemic cells. In vitro assays further demonstrated that 1-methoxyerythrabyssin II promoted autophagy and suppressed cell proliferation by inhibiting the PI3K/Akt/mTOR pathway in leukemic cells. This discovery will contribute to the development of novel therapeutics and prophylactics against leukemia.

Key words

MET - leukemia - PI3K/Akt/mTOR pathway - Lespedeza bicolor - Fabaceae

* Co-corresponding authors.


Supporting Information



Publication History

Received: 25 July 2022

Accepted after revision: 13 June 2023

Article published online:
17 July 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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