Shikonin suppresses proliferation and induces apoptosis in human leukemia NB4 cells through modulation of MAPKs and c‑Myc

Mol Med Rep. 2017 Sep;16(3):3055-3060. doi: 10.3892/mmr.2017.6965. Epub 2017 Jul 13.


Acute promyelocytic leukemia (APL) is a special subtype of acute myeloid leukemia that responds to treatment with all‑trans retinoic acid and arsenic trioxide. However, severe side effects and drug resistance limit the effectiveness of these treatments. Hence, new drugs for APL are required urgently. Shikonin, an active naphthoquinone derived from the Chinese medical herb Zi Cao exerts antitumor activity in several cancers. In the present study, the effects of shikonin on proliferation and apoptosis in NB4 cells, as well as related mechanisms were assessed. Treatment of NB4 cells with shikonin inhibited proliferation in a concentration‑ and time‑dependent manner. The cell cycle was arrested in the G1 phase. NB4 cells treated with shikonin exhibited more apoptosis and higher levels of cleaved caspase‑3 and poly ADP‑ribose polymerase than control cells. Western blotting results demonstrated that the expression of p‑p38 mitogen‑activated protein kinase (p‑p38MAPK) and p‑c‑Jun N‑terminal kinase (p‑JNK) was increased significantly by shikonin treatment, while the expression of p‑ERK and c‑Myc was decreased. In summary, these findings indicated that shikonin inhibited cell proliferation and induced apoptosis partly through modulation of the MAPKs and downregulation of c‑Myc.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Nucleus Shape / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Humans
  • Leukemia, Promyelocytic, Acute / enzymology*
  • Leukemia, Promyelocytic, Acute / pathology*
  • Microscopy, Fluorescence
  • Mitogen-Activated Protein Kinases / metabolism*
  • Naphthoquinones / pharmacology*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism*


  • Naphthoquinones
  • Proto-Oncogene Proteins c-myc
  • shikonin
  • Poly(ADP-ribose) Polymerases
  • Mitogen-Activated Protein Kinases
  • Caspase 3