糖酵解参与调控楝酰胺抑制慢性粒细胞白血病细胞增殖的研究

doi:10.16333/j.1001-6880.2024.5.009

天然产物研究与开发 ›› 2024, Vol. 36 ›› Issue (5): 798-804.doi: 10.16333/j.1001-6880.2024.5.009

糖酵解参与调控楝酰胺抑制慢性粒细胞白血病细胞增殖的研究

曾玲芝1,3，王春林4,5，刘务玲4,5，杨奕樱2,3，李艳梅4,5*，宋佳蕾2,3*

1贵州中医药大学药学院；2贵州中医药大学基础医学院；3贵州中医药大学分子生物学重点实验室，贵阳 550025；4贵州省中国科学院天然产物化学重点实验室；5贵州医科大学省部共建药用植物功效与利用国家重点实验室，贵阳 550014

出版日期:2024-05-28 发布日期:2024-05-29
基金资助:
国家自然科学基金地区项目（82260854，81960546）；贵州省科技计划（黔科合基础-ZK［2022］一般485,黔科合基础-ZK［2023］一般240）；贵州省教育厅青年科技人才成长项目（黔教合KY字［2022］267号）

Rocaglamide inhibits the proliferation of chronic myelogenous leukemia cells partly via aerobic glycolysis

ZENG Ling-zhi1,3,WANG Chun-lin4,5,LIU Wu-ling4,5,YANG Yi-ying2,3,LI Yan-mei4,5*,SONG Jia-lei2,3*

1School of Pharmacy,Guizhou University of Traditional Chinese Medicine;2School of Basic Medicine,Guizhou University of Traditional Chinese Medicine;3The Key Laboratory of Molecular Biology,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;4The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences;5State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guiyang 550014,China

Online:2024-05-28 Published:2024-05-29

摘要/Abstract

摘要： 本研究旨在探讨糖酵解参与楝酰胺的抗慢性粒细胞白血病细胞活性及机制。研究发现，楝酰胺以时间和浓度依赖性抑制K562细胞的生长增殖，其作用于K562细胞3 d的IC₅₀为21.70±5.68 nmol/L。楝酰胺阻滞K562细胞于G2/M期，诱导出现凋亡。楝酰胺降低了K562细胞的葡萄糖消耗量和乳酸生成水平，抑制c-Myc和己糖激酶2（hexokinase 2，HK2）的蛋白表达。K562细胞在进行去葡萄糖处理后生长减慢，乳酸生成水平降低，c-Myc蛋白表达下调。楝酰胺在无葡萄糖培养下K562细胞上的抑制率明显低于含葡萄糖培养下K562细胞上的抑制率。以上结果说明楝酰胺具有抗慢性粒细胞白血病细胞活性，其作用机制可能是抑制c-Myc和HK2介导的糖酵解。

关键词: 楝酰胺, 慢性粒细胞白血病, 糖酵解, c-Myc, HK2

Abstract:

To explore the anti-chronic myelogenous leukemia (CML) activity of rocaglamide (RocA) caused by aerobic glycolysis and potent molecular mechanism,the proliferation of CML cell line K562 inhibited by RocA were determined.The MTT assay showed that RocA inhibited the proliferation of K562 in a time-and dose-dependent way.The IC50 of K562 treated with RocA for 3 days was 21.70±5.68 nmol/L.Flow cytometry analyzed that the proportion of cells of G2/M phase was significantly increased.The apoptotic cells was significantly increased.RocA decreased the glucose consumption,lactate acid production and the protein expression of hexokinase 2 (HK2),c-Myc,which take an important part in aerobic glycolysis.The propagation rate,lactate acid production and the c-Myc protein expressionof K562 cells cultured without glucose was significantly lower than that cultured with glucose.After treatment with RocA,the inhibition on K562 cells cultured without glucose was significantly decreased compared to K562 cells cultured with glucose.Taken together,we presumed that RocA inhibited the proliferation of CML cells via apoptosis induction and cycle arrest partly through c-Myc/HK2 mediated aerobic glycolysis suppression.

Key words: rocaglamide, chronic myelogenous leukemia, aerobic glycolysis, c-Myc, HK2

中图分类号: R932

曾玲芝, 王春林, 刘务玲, 杨奕樱, 李艳梅, 宋佳蕾. 糖酵解参与调控楝酰胺抑制慢性粒细胞白血病细胞增殖的研究[J]. 天然产物研究与开发, 2024, 36(5): 798-804.

ZENG Ling-zhi, WANG Chun-lin, LIU Wu-ling, YANG Yi-ying, LI Yan-mei, SONG Jia-lei. Rocaglamide inhibits the proliferation of chronic myelogenous leukemia cells partly via aerobic glycolysis[J]. NATURAL PRODUCT RESEARCH AND DEVELOPMENT, 2024, 36(5): 798-804.

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糖酵解参与调控楝酰胺抑制慢性粒细胞白血病细胞增殖的研究

Rocaglamide inhibits the proliferation of chronic myelogenous leukemia cells partly via aerobic glycolysis

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