Matrine inhibits BCR/ABL mediated ERK/MAPK pathway in human leukemia cells

Oncotarget
Ling-di MaChang Zou

Abstract

The BCR/ABL fusion gene and its downstream signaling pathways such as Ras/Raf/MAPK, JAK/STAT3, and PI3K/AKT pathways play important roles in malignant transformation of leukemia, especially chronic myelogenous leukemia (CML). Our previous study showed that matrine, an alkaloid extracted from a Chinese herb radix sophorae, significantly inhibited the proliferation of human CML K562cells, induced cell cycle arrest in G0/G1, and promoted cell apoptosis. In the present study, we investigated the molecular mechanism of matrine in the growth inhibition of leukemia cells using K562 and HL-60 cell lines. RT-PCR and Western blot assay demonstrated that the expression of BCR/ABL in K562 and HL-60 cells was significantly inhibited by matrine treatment. Phosphorylation of MEK1, ERK1/2, and their upstream adaptor molecules Shc and SHP2 were significantly downregulated. The protein and mRNA expression of components of the ERK/MAPK signal pathway, and Bcl-xL, Cyclin D1, and c-Myc, were dramatically reduced. Conversely, the expression of p27, a negative regulator of cell cycle progression, increased after matrine treatment. These results indicated that the inhibition of ERK/MAPK and BCR/ABL signaling pathway was associated with matrine's suppr...Continue Reading

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Citations

Nov 7, 2019·Cancers·Kelsey L PolakMark W Jackson
May 27, 2021·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Siya SunYuqing Ge
Jun 8, 2021·Molecular Therapy Oncolytics·Zhixia ZhouPeifeng Li

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Methods Mentioned

BETA
protein exchange
PCR
Protein Assay
X-ray

Software Mentioned

SPSS
Qgene

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