2. Academic Validation
  3. Antileukemic effect of caffeic acid 3,4-dihydroxyphenetyl ester. Evidences for its mechanisms of action

Antileukemic effect of caffeic acid 3,4-dihydroxyphenetyl ester. Evidences for its mechanisms of action

  • Phytomedicine. 2021 Jan;80:153383. doi: 10.1016/j.phymed.2020.153383.
Mingmin Tang 1,  Xin Xie 2,  Muran Shi 1,  Wenxiu Xin 3,  Guowan Zheng 1,  Yanhua Zhang 1,  Zhizhen Zhang 4,  Xiaoyuan Lian 5
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
  • 2 Zhejiang Center for Medical Device Evaluation, Hangzhou 310009, China.
  • 3 Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou 310022, China.
  • 4 Ocean College, Zhoushan Campus, Zhejiang University, Zhoushan 316021, China. Electronic address: zzhang88@zju.edu.cn.
  • 5 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. Electronic address: xylian@zju.edu.cn.
PMID: 33091855 DOI: 10.1016/j.phymed.2020.153383
Abstract

Background: Caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) is a natural polyphenolic ester isolated as a minor component from a water extract of the Chinese medicine Zhongjiefeng [Sarcandra glabra (Thunb.) Nakai (Chloranthaceae)] and has previously shown to have activity against solid tumors through the modulation of multiple targets or signal pathways. However, the activity and potential mechanism of CADPE against leukemia cells have not yet been characterized.

Purpose: To investigate whether and how CADPE kills leukemia cells.

Method: (1) The activity of CADPE inhibiting the growth of different leukemia cell lines was evaluated by MTT assay; (2) Cell cycle arrest and Apoptosis induced by CADPE were determined by flow cytometry with FlowJo software for quantification; (3) The protein levels were analyzed by Western blot and ubiquitin-binding c-Myc was acquired by co-immunoprecipitation.

Results: CADPE exerted potent activity against different leukemia cell lines with low toxicity in normal cells. In terms of mechanism of action, CADPE promoted ubiquitin-proteasome-dependent degradation of c-Myc through activating glycogen synthase kinase-3β (GSK3β) and downregulating deubiquitinating Enzyme USP28 to trigger the interaction of c-Myc with ubiquitin Ligase Fbw7, resulting in the downregulation of cell cycle regulators and anti-apoptotic proteins and consequently, cell cycle arrest and cell Apoptosis.

Conclusion: CADPE is a novel c-Myc Inhibitor with high activity and a unique mechanism for killing leukemia cells.

Keywords

CADPE; Fbw7; GSK3β; Leukemia cells; USP28; c-Myc; ubiquitin degradation.

Figures
Products