Matrine suppresses cell growth of human chronic myeloid leukemia cells via its inhibition of the interleukin-6/Janus activated kinase/signal transducer and activator of transcription 3 signaling cohort

Leuk Lymphoma. 2015;56(10):2923-30. doi: 10.3109/10428194.2015.1007507. Epub 2015 Mar 11.

Abstract

Matrine, alkaloid isolated from Sophora flavescens, is known to be pleiotropic by exerting anti-inflammatory, anti-oxidation, as well as anti-cancer effects. However, the precise molecular targets or pathways responsible for its activities still remain unclear. The present study aimed to determine the underlying mechanisms of matrine in inhibiting the chronic myeloid leukemia cells (CML). It was observed that matrine treatment significantly suppressed CML cells proliferation, induced apoptosis and resulted in the accumulation of cells in the G0/G1 phase, accompanied by a significant decrease in Bcl-xL, Cyclin D1, and c-Myc expression. Western blot analyses revealed that matrine treatment resulted in the down-regulation in phospho-STAT3 and phospho-JAK2 without significantly effects on STAT3 and JAK2 protein levels. Matrine significantly reduced the expression of IL-6, a potent upstream activating factor of STAT3. These results strongly suggested the IL-6/JAK/STAT3 pathway play an important role in matrine's anti-leukemia effects in K562 cells.

Keywords: CML; IL-6; JAK/STAT3 pathway; K562 cell; Matrine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Janus Kinases / metabolism*
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Matrines
  • Quinolizines / pharmacology*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Interleukin-6
  • Quinolizines
  • STAT3 Transcription Factor
  • Janus Kinases
  • Matrines