PMID- 17506948
OWN - NLM
STAT- MEDLINE
DCOM- 20090420
LR  - 20121115
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 28
IP  - 6
DP  - 2007 Jun
TI  - Mitochondrial-derived ROS in edelfosine-induced apoptosis in yeasts and tumor 
      cells.
PG  - 888-94
AB  - AIM: To investigate whether a similar process mediates cytotoxicity of 
      1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3, edelfosine) in 
      both yeasts and human tumor cells. METHODS: A modified version of a previously 
      described assay for the intracellular conversion of nitro blue tetrazolium to 
      formazan by superoxide anion was used to measure the generation of reactive 
      oxygen species (ROS). Apoptotic yeast cells were detected using terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. DNA 
      fragmentation and the generation of ROS were measured by cytofluorimetric 
      analysis in Jurkat cells. RESULTS: Edelfosine induced apoptosis in Saccharomyces 
      cerevisiae, as assessed by TUNEL assay. Meanwhile, edelfosine induced a time- and 
      concentration-dependent generation of ROS in yeasts. Rotenone, an inhibitor of 
      the mitochondrial electron transport chain, prevented ROS generation and 
      apoptosis in response to edelfosine in S cerevisiae. alpha-Tocopherol abrogated 
      the edelfosine-induced generation of intracellular ROS and apoptosis. Edelfosine 
      also induced an increase of ROS in human leukemic cells that preceded apoptosis. 
      The overexpression of Bcl-2 by gene transfer abrogated both ROS generation and 
      apoptosis induced by edelfosine in leukemic cells. Changes in the relative 
      mitochondrial membrane potential were detected in both yeasts and Jurkat cells. 
      CONCLUSION: These results indicate that edelfosine induces apoptosis in yeasts in 
      addition to human tumor cells, and this apoptotic process involves mitochondria, 
      likely through mitochondrial-derived ROS. These data also suggest that yeasts can 
      be used as a suitable cell model in elucidating the antitumor mechanism of action 
      of edelfosine.
FAU - Zhang, Hui
AU  - Zhang H
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Central South 
      University, Changsha 410078, China.
FAU - Gajate, Consuelo
AU  - Gajate C
FAU - Yu, Li-Ping
AU  - Yu LP
FAU - Fang, Yun-Xiang
AU  - Fang YX
FAU - Mollinedo, Faustino
AU  - Mollinedo F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Phospholipid Ethers)
RN  - 0 (Reactive Oxygen Species)
RN  - 1Y6SNA8L5S (edelfosine)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/*drug effects
MH  - *Cell Line, Tumor/drug effects/physiology
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Membrane Potential, Mitochondrial/drug effects/physiology
MH  - Mitochondria/*metabolism
MH  - Phospholipid Ethers/*pharmacology
MH  - Reactive Oxygen Species/*metabolism
MH  - *Saccharomyces cerevisiae/cytology/drug effects/metabolism
EDAT- 2007/05/18 09:00
MHDA- 2009/04/21 09:00
CRDT- 2007/05/18 09:00
PHST- 2007/05/18 09:00 [pubmed]
PHST- 2009/04/21 09:00 [medline]
PHST- 2007/05/18 09:00 [entrez]
AID - 10.1111/j.1745-7254.2007.00568.x [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2007 Jun;28(6):888-94. doi: 10.1111/j.1745-7254.2007.00568.x.