HPLC analysis of harringtonine and homoharringtonine in the needles of Cephalotaxus griffithii alkaloid fraction and cytotoxic activity on chronic myelogenous leukaemia K562 cell

Nat Prod Res. 2014;28(18):1503-6. doi: 10.1080/14786419.2014.913241. Epub 2014 Apr 30.

Abstract

Harringtonine (HT) and homoharringtonine (HHT) are Cephalotaxus alkaloids with considerable antileukaemic activity. The objectives of this research were to (1) determine the content of HT and HHT present in Cephalotaxus griffithii needles alkaloid fraction (CGAF) and (2) compare the antiproliferative activity of CGAF, with that of HT and HHT on chronic myelogenous leukaemia K562 cell. The concentration of HT and HHT was found to be 122.14 and 16.79 mg/g of CGAF, respectively. Treatment of K562 cells with CGAF, HT and HHT decreased the viable cells in a dose- and time-dependent manner. Interestingly, the maximum cell death was found in CGAF, with IC50 value which was 3- to 4.6-fold lower than those of HT and HHT. Our results indicate that HT content in the needles of C. griffithii is higher than HHT, and alkaloids other than HT and HHT in CGAF are predominantly responsible for K562 cell death.

Keywords: Cephalotaxus griffithii; K562; harringtonine; homoharringtonine; leukaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Cephalotaxus / chemistry*
  • Chromatography, High Pressure Liquid
  • Drug Screening Assays, Antitumor
  • Harringtonines / analysis*
  • Harringtonines / chemistry
  • Homoharringtonine
  • Humans
  • Inhibitory Concentration 50
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Substances

  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Harringtonines
  • harringtonin
  • Homoharringtonine