Curcuminoid-phospholipid complex induces apoptosis in mammary epithelial cells by STAT-3 signaling.
Curcumin (from the rhizome of Curcuma longa) is well documented for its medicinal properties in Indian and Chinese systems of medicine where it is widely used for the treatment of several diseases. Epidemiological observations are suggestive that curcumin consumption may reduce the risk of some form of cancers and provide other protective biological effects in humans. These biological properties have been attributed to curcuminoids that have been widely studied for their anti-inflammatory, anti-angiogenic, antioxidant, wound healing and anti-cancer effects. In this study we have investigated on the effect of a curcumin phospholipid complex on mammary epithelial cell viability. HC11 and BME-UV cell lines, validated models to study biology of normal, not tumoral, mammary epithelial cells, were used to analyse these effects. We report that curcumin acts on STAT-3 signal pathway to reduce cell viability and increase apoptosis evaluated by the the amount of activated caspase 3. Further it reduces MAPK and AKT activations. JSI-124, a STAT-3 inhibitor (100 nM) was able to block the negative effect of curcumin on cell viability and caspase 3 activation. Finally the negative effect of cucumin on cell viability has been impaired in STAT-3i HC11, where STAT-3 protein was greatly reduced by shRNA-interference. These results indicate that curcumin presents a potential adverse effect to normal mammary epithelial cells and that it has a specific effect on signal trasduction in mammary epithelium.
Starvaggi Cucuzza
Laura
L
Department of Veterinary Morphophysiology, Via Leonardo da Vinci 44, 10095, Grugliasco 10095, University of Torino, Torino, Italy.
Motta
Massimiliano
M
Miretti
Silvia
S
Accornero
Paolo
P
Baratta
Mario
M
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000009:adverse effects*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008321:Mammary Glands, Animal / Q000166:cytology; D051379:Mice; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014315:Triterpenes / Q000494:pharmacology
D010743:Phospholipids; D050796:STAT3 Transcription Factor; D014315:Triterpenes; D051058:Oncogene Protein v-akt; C505409:Casp3 protein, mouse; D053148:Caspase 3; D003474:Curcumin; C038106:cucurbitacin I