Mitogenic effects of phosphatidylcholine nanoparticles on MCF-7 breast cancer cells.
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.
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Yamila B
YB
Gándola
Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Sebastián E
SE
Pérez
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Pablo E
PE
Irene
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Ana I
AI
Sotelo
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Johanna G
JG
Miquet
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Gerardo R
GR
Corradi
Departamento de Tecnología Farmacéutica, Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Adriana M
AM
Carlucci
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Junín 956, 1113 Buenos Aires, Argentina.
Lorena
L
Gonzalez
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008934:Mitogens / Q000737:chemistry / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000494:pharmacology
D008934:Mitogens; D009363:Neoplasm Proteins; D010713:Phosphatidylcholines; C512478:EGFR protein, human; D066246:ErbB Receptors