Curcuminoid-phospholipid complex induces apoptosis in mammary epithelial cells by STAT-3 signaling

Abstract

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-3 i 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.

Curcumin―The Paradigm of a Multi-Target Natural Compound with Applications in Cancer Prevention and Treatment

“…When used as a pre-treatment, curcumin inhibits interferon-gamma-induced phosphorylation of nuclear STAT1 and -3 [ 63 , 64 ]. Similar suppression of STAT3 activation was also observed in Hodgkin’s lymphoma [ 52 ], T-cell leukemia [ 65 ], head and neck squamous cell carcinoma [ 66 ], multiple myeloma cells [ 52 , 67 ] and in CD138 + cells derived from multiple myeloma patients [ 45 ] following curcumin treatment but also after treatment with curcumin analogs such as GO-Y030 [ 68 ], FLLL1 and FLLL12 [ 69 ] or a curcumin-phospholipid complex [ 70 ]. The interferon-a-induced activation of STAT1 was also inhibited by curcumin in human lung A549 carcinoma and melanoma cells [ 71 ].…”

Curcumin induces p53-independent inactivation of Nrf2 during oxidative stress–induced apoptosis

“…Curcumin is a known inducer of apoptosis in different types of normal and tumoral cells. [42][43][44][45][46][47][48][49] Importantly, previous studies showed that curcumin may induce apoptosis in EBV-immortalized lymphoblastoid cells. 50 Thus, we first corroborated the proapoptotic properties of curcumin in CL-45 cells and found that the phytochemical induced cell death in a dose-dependent manner.…”

Characterization of Curcuminoid from Curcuma xanthorrhiza and Its Activity Test as Antioxidant and Antibacterial

“…Several studies have been carried out on rhizome of C. domestica, C. longa, C.xanthorrhiza, and C. zedoaria shows the presence of curcumin derivatives and sesquiterpen compounds (Cucuzza, Motta, Miretti, Accornero, & Baratta, 2008). Curcuminoids contained in several species depending on the type of species.…”