BioMed Research International · 2014 · 39 citations · 27 references
PharmacyOncologyPharmaceuticsCell SignalingDrug DeliveryMembrane TraffickingCancer NanomedicineLipid-based NanoparticlesNanocarriers For TherapeuticsNanomaterials For Drug DeliveryNanomedicineNanoparticle FormulationsCancer NanotherapyEpidermal Growth Factor Receptor InhibitionEpidermal Growth Factor Receptor SignalingLipid Nanoparticle Delivery SystemsMitogenic Signaling PathwaysNanoparticle DeliveryNanoparticle-membrane InteractionsNanoparticles
Lecithins, mainly composed of the phospholipids phosphatidylcholines (PC), have many different uses in the pharmaceutical and clinical field. PC are involved in structural and biological functions as membrane trafficking processes and cellular signaling. Considering the increasing applications of lecithin-based nanosystems for the delivery of therapeutic agents, the aim of the present work was to determine the effects of phosphatidylcholine nanoparticles over breast cancer cellular proliferation and signaling. PC dispersions at 0.01 and 0.1% (w/v) prepared in buffer pH 7.0 and 5.0 were studied in the MCF-7 breast cancer cell line. Neutral 0.1% PC-derived nanoparticles induced the activation of the MEK-ERK1/2 pathway, increased cell viability and induced a 1.2 fold raise in proliferation. These biological effects correlated with the increase of epidermal growth factor receptor (EGFR) content and its altered cellular localization. Results suggest that nanoparticles derived from PC dispersion prepared in buffer pH 7.0 may induce physicochemical changes in the plasma membrane of cancer cells which may affect EGFR cellular localization and/or activity, increasing activation of the MEK-ERK1/2 pathway and inducing proliferation. Results from the present study suggest that possible biological effects of delivery systems based on lecithin nanoparticles should be taken into account in pharmaceutical formulation design.
27
An Allosteric Mechanism for Activation of the Kinase Domain of Epidermal Growth Factor Receptor
Xuewu Zhang, Jodi Gureasko, Kui Shen et al. · Cell · 2006 · 1.6K citations · Full text
Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling
Yimin Fang, Montserrat Vilella-Bach, Rebecca Bachmann et al. · Science · 2001 · 1.1K citations