Andrographolide Suppresses MV4-11 Cell Proliferation through the Inhibition of FLT3 Signaling, Fatty Acid Synthesis and Cellular Iron Uptake

Molecules

Teck Kwang Lim¹  Jigang Wang¹  Qingsong Lin¹  Yin Kwan Wong¹  Yifei Lay¹  Jianbin Zhang²  Chye Sun Ong³  Lixia Yuan⁴  Xiao Chen⁵  Zichun Hua⁵ 

[1] Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore;Department of Oncology, Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China;Institute of Mental Health, Education Office, Singapore 539747, Singapore;School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China;The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China;

关键词: andrographolide;    fatty acid synthesis;    FLT3 signaling;    intracellular iron pool;    MV4-11;    protein synthesis;    quantitative proteomics;   

DOI  :  10.3390/molecules22091444

来源: DOAJ

【 摘 要 】

Background: Andrographolide (ADR), the main active component of Andrographis paniculata, displays anticancer activity in various cancer cell lines, among which leukemia cell lines exhibit the highest sensitivity to ADR. In particular, ADR was also reported to have reduced drug resistance in multidrug resistant cell lines. However, the mechanism of action (MOA) of ADR’s anticancer and anti-drug-resistance activities remain elusive. Methods: In this study, we used the MV4-11 cell line, a FLT3 positive acute myeloid leukemia (AML) cell line that displays multidrug resistance, as our experimental system. We first evaluated the effect of ADR on MV4-11 cell proliferation. Then, a quantitative proteomics approach was applied to identify differentially expressed proteins in ADR-treated MV4-11 cells. Finally, cellular processes and signal pathways affected by ADR in MV4-11 cell were predicted with proteomic analysis and validated with in vitro assays. Results: ADR inhibits MV4-11 cell proliferation in a dose- and time-dependent manner. With a proteomic approach, we discovered that ADR inhibited fatty acid synthesis, cellular iron uptake and FLT3 signaling pathway in MV4-11 cells. Conclusions: ADR inhibits MV4-11 cell proliferation through inhibition of fatty acid synthesis, iron uptake and protein synthesis. Furthermore, ADR reduces drug resistance by blocking FLT3 signaling.

【 授权许可】

Unknown