Apoptosis of human carcinoma of mouth floor KB cells and multidrug resistant KBv200 cells induced by azide methyl anthraquinone derivative.
- Author:
Yan DING
1
;
Li-rong HE
;
Ka-jia CAO
;
Yu LU
;
Lian-quan GU
;
Li-wu FU
Author Information
- Publication Type:Journal Article
- MeSH: Anthraquinones; administration & dosage; chemistry; pharmacology; Antineoplastic Agents; administration & dosage; chemistry; pharmacology; Apoptosis; drug effects; Cell Proliferation; drug effects; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; KB Cells; Mitochondria; physiology; Molecular Structure; Mouth Floor; Mouth Neoplasms; pathology; Reactive Oxygen Species; metabolism; Vincristine; pharmacology
- From: Acta Pharmaceutica Sinica 2005;40(1):22-26
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo determine the effects of azide methyl anthraquinone derivative (AMAD) on growth inhibition and inducing apoptosis of multidrug resistant (MDR) KBv200 cells and parental drug-sensitive KB cells.
METHODSCytotoxicity was determined by tetrazolium (MTF) assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (deltapsi(m)) in cells were labeled with DCFH-DA and DiOC6 and tested by flow cytometry. Annexin V stain and DNA ladder were used to examine the apoptosis of KB and KBv200 cells induced by AMAD.
RESULTSAMAD was shown to inhibit the growth of KB and KBv200 cells significantly in a concentration-dependent manner, with mean IC50 of 0.36 and 0.45 micromol x L(-1), respectively. The generation of ROS increased obviously after the cells were treated with AMAD for 12 h, up to the peak in 24 h, meanwhile the levels of deltapsi(m) were time-dependently decreased. DNA fragmentation appeared on the agarose gel. Annexin V stain showed AMAD induced apoptosis of KB and KBv200 cells also in a concentration-dependent manner.
CONCLUSIONAMAD showed inhibitory effect on both MDR KBv200 cells and parental drug-sensitive KB cells. The mechanism of action was associated with the increase of the cellular ROS level and the decrease of the mitochondrial membrane potential induced by AMAD, which result in cell apoptosis.
