Journal article
The mechanism of methylselenocysteine and docetaxel synergistic activity in prostate cancer cells
Molecular cancer therapeutics, Vol.5(10), pp.2540-2548
10/01/2006
DOI: 10.1158/1535-7163.MCT-05-0546
PMCID: PMC2826137
PMID: 17041098
Abstract
The study was designed to evaluate the combination treatment of methylselenocysteine (MSeC) and docetaxel and to delineate the underlying mechanism associated with observed
in vitro
synergy between MSeC and docetaxel in prostate cancer cells. Cells were treated with different concentrations and schedules (concurrent or sequential) of MSeC and docetaxel alone or in combination. Cell growth/death was assessed with sulforhodamine B assay, trypan blue assay, and time-lapse video. Loewe synergism/antagonism model was used to determine whether the combination effect was additive, synergistic, or antagonistic. Apoptosis and caspase-3 activity were evaluated with cell death ELISA assay and caspase activity assay, respectively. Synergy between MSeC and docetaxel was further assessed in the presence and absence of z-VAD-fmk, a pan-caspase inhibitor. Effect of MSeC and docetaxel alone or in combination on the cellular expression of the antiapoptotic protein survivin was measured with Western blot analyses. Pretreatment with MSeC was crucial to enhance docetaxel antitumor activity. The enhanced antitumor activity of the sequential combination treatment of MSeC and docetaxel (MSeC/docetaxel) was highly synergistic. Apoptosis increased after MSeC/docetaxel, compared with each drug alone or concurrent treatment. Pretreatment with z-VAD-fmk converted the synergy into antagonism, suggesting that the synergy is caspase-dependent apoptosis. The survivin level was down-regulated following MSeC/docetaxel treatment when compared with each drug alone. In conclusion, pretreatment with MSeC was essential to markedly sensitize cells to docetaxel. The synergy between MSeC and docetaxel in C2G prostate cancer cells is associated with increased level of caspase-dependent apoptosis and decreased level of survivin.
Details
- Title: Subtitle
- The mechanism of methylselenocysteine and docetaxel synergistic activity in prostate cancer cells
- Creators
- Rami G. Azrak - Roswell Park Cancer InstituteCheryl L. Frank - Roswell Park Cancer InstituteXiang Ling - Roswell Park Cancer InstituteHarry K. Slocum - Roswell Park Cancer InstituteFengzhi Li - Roswell Park Cancer InstituteBarbara A. Foster - Roswell Park Cancer InstituteYoucef M. Rustum - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Molecular cancer therapeutics, Vol.5(10), pp.2540-2548
- DOI
- 10.1158/1535-7163.MCT-05-0546
- PMID
- 17041098
- PMCID
- PMC2826137
- ISSN
- 1535-7163
- eISSN
- 1538-8514
- Language
- English
- Date published
- 10/01/2006
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359883202771
Metrics
9 Record Views