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

• Published in: Molecules (Basel, Switzerland) Vol. 22; no. 9; p. 1444
• Main Authors: Chen, Xiao, Zhang, Jianbin, Yuan, Lixia, Lay, Yifei, Wong, Yin Kwan, Lim, Teck Kwang, Ong, Chye Sun, Lin, Qingsong, Wang, Jigang, Hua, Zichun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31.08.2017; MDPI
• Subjects: Acute myeloid leukemia; andrographolide; Antineoplastic Agents - pharmacology; Antitumor activity; Biotechnology; Cancer; Cell growth; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Diterpenes - pharmacology; Drug resistance; Drug Screening Assays, Antitumor; fatty acid synthesis; Fatty acids; Fatty Acids - biosynthesis; FLT3 signaling; fms-Like Tyrosine Kinase 3 - metabolism; Humans; Inhibition; intracellular iron pool; Iron; Iron - metabolism; Kinases; Leukemia; Multidrug resistance; MV4-11; Myeloid leukemia; Protein biosynthesis; Protein Biosynthesis - drug effects; Protein synthesis; Proteins; Proteomics; quantitative proteomics; Signal processing; Signal transduction; Signal Transduction - drug effects; Tumor cell lines; FLT3 signaling; fatty acid synthesis; intracellular iron pool; protein synthesis; MV4-11; quantitative proteomics; andrographolide
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules22091444

: Andrographolide (ADR), the main active component of , 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. : 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. : 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. : 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.