Lycorine induces apoptosis and down-regulation of Mcl-1 in human leukemia cells

Cancer Lett. 2009 Feb 8;274(1):16-24. doi: 10.1016/j.canlet.2008.08.029. Epub 2008 Sep 30.

Abstract

Lycorine is an alkaloid isolated from the bulb of the Amaryllidaceae Lycoris. Here, we report that treatment with lycorine resulted in survival inhibition and apoptosis induction in human leukemia cell lines. Lycorine induced apoptosis in human leukemia cells via intrinsic mitochondria pathway and caused a rapid-turnover of protein level of Mcl-1 which occurred before caspases activation. Furthermore, pronounced apoptosis accompanied by the down-regulation of Mcl-1 was also observed in blasts from patients with acute myeloid leukemia. Our findings suggest that lycorine may be a good candidate therapeutic agent against leukemia in worth of further evaluation.

MeSH terms

  • Amaryllidaceae Alkaloids / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Caspases / metabolism
  • Cytochromes c / metabolism
  • Down-Regulation / drug effects
  • Humans
  • Leukemia / metabolism*
  • Leukemia / pathology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Phenanthridines / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • Amaryllidaceae Alkaloids
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Phenanthridines
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Cytochromes c
  • Caspases
  • lycorine