Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis.
BACKGROUND
Epidemiologic studies suggest that diets high in fruits and vegetables reduce cancer risk. Resveratrol, a compound present in grapes, has been shown to inhibit a variety of primary tumors. Pterostilbene, an analogue of resveratrol found in blueberries, has both antioxidant and antiproliferative properties. We hypothesized that pterostilbene would induce apoptosis and inhibit breast cancer cell growth in vitro.


METHODS
Breast cancer cells were treated with graduated doses of pterostilbene. Cell viability was measured by MTT assay. Apoptosis was evaluated via DNA fragmentation assay and TUNEL assay. Apo-ONE caspase-3/7 assay was used to evaluate caspase activity. Flow cytometry was used to evaluate mitochondrial depolarization, superoxide formation, and cell cycle. Student's t-test and two-way ANOVA with Bonferroni posttests were utilized for statistical analysis.


RESULTS
Pterostilbene decreased breast cancer cell viability in a concentration- and time-dependent manner. Pterostilbene treatment increased caspase-3/7 activity and apoptosis in both cell lines. Caspase-3/7 inhibitors completely reversed pterostilbene's effects on cell viability. Pterostilbene treatment triggered mitochondrial depolarization, increased superoxide anion, and caused alteration in cell cycle.


CONCLUSIONS
Pterostilbene treatment inhibits the growth of breast cancer in vitro through caspase-dependent apoptosis. Mitochondrial membrane depolarization and increased superoxide anion may contribute to the activation downstream effector caspases. Caspase inhibition leads to complete reversal of pterostilbene's effect on cell viability. Further in vitro mechanistic studies and in vivo experiments are warranted to determine its potential for the treatment of breast cancer.
Alosi
Julie A
JA
University of Vermont, Burlington, Vermont, USA.
McDonald
Debbie E
DE
Schneider
John S
JS
Privette
Alicia R
AR
McFadden
David W
DW
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D061945:Caspase Inhibitors; D020169:Caspases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005638:Fruit; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D010936:Plant Extracts / Q000627:therapeutic use; D035721:Pterocarpus; D013267:Stilbenes / Q000627:therapeutic use*; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D061945:Caspase Inhibitors; D010936:Plant Extracts; D013267:Stilbenes; D013481:Superoxides; C107773:pterostilbene; D020169:Caspases