Molecular evidence of anti-leukemia activity of gypenosides on human myeloid leukemia HL-60 cells in vitro and in vivo using a HL-60 cells murine xenograft model

Phytomedicine. 2011 Sep 15;18(12):1075-85. doi: 10.1016/j.phymed.2011.03.009. Epub 2011 May 18.

Abstract

We have shown that gypenosides (Gyp) induced cell cycle arrest and apoptosis in many human cancer cell lines. However, there are no reports showing that show Gyp acts on human leukemia HL-60 cells in vitro and in a murine xenograft model in vivo. In the present study effects of Gyp on cell morphological changes and viability, cell cycle arrest and induction of apoptosis in vitro and effects on Gyp in an in vivo murine xenograft model. Results indicated that Gyp induced morphological changes, decreased cell viability, induced G0/G1 arrest, DNA fragmentation and apoptosis (sub-G1 phase) in HL-60 cells. Gyp increased reactive oxygen species production and Ca(2+) levels but reduced mitochondrial membrane potential in a dose- and time-dependent manner. Gyp also changed one of the primary indicators of endoplasmic reticulum (ER) stress due to the promotion of ATF6-α and ATF4-α associated with Ca(2+) release. Gyp reduced the ratio of Bcl-2 to Bax due to an increase in the pro-apoptotic protein Bax and inhibited levels of the anti-apoptotic protein Bcl-2. Oral consumption of Gyp reduced tumor size of HL-60 cell xenograft mode mice in vivo. These results provide new information on understanding mechanisms by which Gyp induces cell cycle arrest and apoptosis in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / analysis*
  • Apoptosis / drug effects*
  • Calcium / metabolism
  • Caspases / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Damage
  • DNA Fragmentation
  • Gynostemma / chemistry*
  • Humans
  • Leukemia, Experimental / drug therapy*
  • Membrane Potential, Mitochondrial
  • Mice
  • Phytotherapy*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Reactive Oxygen Species / metabolism
  • Transcription Factor CHOP / metabolism
  • Transcription Factors / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • DDIT3 protein, human
  • GTF2A1L protein, human
  • Plant Extracts
  • Reactive Oxygen Species
  • Transcription Factors
  • gypenoside
  • Transcription Factor CHOP
  • Caspases
  • Calcium