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.

Leptin enhances STAT-3 phosphorylation in HC11 cell line: effect on cell differentiation and cell viability.

Leptin is produced in the mammary gland by the fat tissue or by the mammary epithelium. The aim of this study was to investigate the role of leptin on mammary epithelial cell differentiation and cell viability. This study was conducted using the mouse mammary epithelial cell line HC11. We show that leptin, synergizes with prolactin to increase beta-casein gene expression during mammary epithelial cell differentiation. This was correlated with increased phosphorylation of the signal transducer and activator of transcription 3 (STAT-3). Inactivating the function of STAT-3 by expression of a short hairpin RNA demonstrated that the effect of leptin on beta-casein expression is mediated by STAT-3. Secondly, cells in which STAT-3 had been inactivated showed increased cell viability compared to controls and were resistant to the negative effect mediated by leptin. Further, leptin triggers apoptosis in mammary epithelial cells cultivated in non-differentiating conditions. Taken together, these results suggest that leptin, by activating STAT-3, may act as a paracrine factor modulating mammary epithelial cell function.