Curcumin analogue, A13, exhibits anti-leukemia effect via inhibiting STAT3

Tumour Biol. 2016 Jul;37(7):9959-66. doi: 10.1007/s13277-016-4861-0. Epub 2016 Jan 27.

Abstract

Abnormal activation of signal transducer and activator of transcription 3 (STAT3) was reported in some leukemia, and inhibition of STAT3 can be the strategy for the leukemia treatment in clinic. In this study, we tested the anti-tumor effect of compound A13, a water-soluble analogue of curcumin, in vitro and in vivo. Herein, we show that A13 was able to reduce the viability of mastocytoma (P815 cells) and reticulum cell sarcoma (A20 cells) as measured by MTS assay. This effect was accompanied by a marked increase in the proportion of apoptotic cells as measured by flow cytometry. Furthermore, Western blot analysis suggested that the anti-leukemia effect of A13 was realized via STAT3 inhibition. In addition, systemic treatment with A13 in the A20-bearing mice for 60 days resulted in a significant improvement of survival rate and marked reduction of liver metastasis. In summary, our data show that the A13 treatment could effectively be applied to acute leukemia via inhibiting STAT3 signaling pathway.

Keywords: Anti-leukemia; Curcumin analogue; STAT3; Water-soluble.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Bone Marrow Transplantation
  • Cell Proliferation / drug effects
  • Curcumin / analogs & derivatives*
  • Curcumin / pharmacology*
  • Flow Cytometry
  • Immunoenzyme Techniques
  • Leukemia / drug therapy*
  • Leukemia / metabolism
  • Leukemia / pathology
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / metabolism
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Mastocytoma / drug therapy*
  • Mastocytoma / metabolism
  • Mastocytoma / pathology
  • Mice
  • Mice, Inbred BALB C
  • Phosphorylation / drug effects
  • STAT3 Transcription Factor / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Curcumin