Wogonin induces cell cycle arrest and erythroid differentiation in imatinib-resistant K562 cells and primary CML cells

Oncotarget. 2014 Sep 30;5(18):8188-201. doi: 10.18632/oncotarget.2340.

Abstract

Wogonin, a flavonoid derived from Scutellaria baicalensis Georgi, has been demonstrated to be highly effective in treating hematologic malignancies. In this study, we investigated the anticancer effects of wogonin on K562 cells, K562 imatinib-resistant cells, and primary patient-derived CML cells. Wogonin up-regulated transcription factor GATA-1 and enhanced binding between GATA-1 and FOG-1, thereby increasing expression of erythroid-differentiation genes. Wogonin also up-regulated the expression of p21 and induced cell cycle arrest. Studies employing benzidine staining and analyses of cell surface markers glycophorin A (GPA) and CD71 indicated that wogonin promoted differentiation of K562, imatinib-resistant K562, and primary patient-derived CML cells. Wogonin also enhanced binding between GATA-1 and MEK, resulting in inhibition of the growth of CML cells. Additionally, in vivo studies showed that wogonin decreased the number of CML cells and prolonged survival of NOD/SCID mice injected with K562 and imatinib-resistant K562 cells. These data suggested that wogonin induces cycle arrest and erythroid differentiation in vitro and inhibits proliferation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Benzamides / pharmacology*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Differentiation / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm*
  • Erythroid Cells / drug effects*
  • Erythroid Cells / pathology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Flavanones / pharmacology*
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / metabolism
  • Humans
  • Imatinib Mesylate
  • K562 Cells
  • Leukemia, Erythroblastic, Acute / drug therapy*
  • Leukemia, Erythroblastic, Acute / genetics
  • Leukemia, Erythroblastic, Acute / metabolism
  • Leukemia, Erythroblastic, Acute / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • MAP Kinase Kinase Kinases / metabolism
  • Mice, Inbred NOD
  • Mice, SCID
  • Nuclear Proteins / metabolism
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrimidines / pharmacology*
  • RNA Interference
  • Signal Transduction / drug effects
  • Time Factors
  • Transcription Factors / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Benzamides
  • Flavanones
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Nuclear Proteins
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Transcription Factors
  • ZFPM1 protein, human
  • Imatinib Mesylate
  • Extracellular Signal-Regulated MAP Kinases
  • MAP Kinase Kinase Kinases
  • wogonin