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Autocrine Growth Hormone (GH) induces cell growth, proliferation metastasis in breast cancer. Curcumin is a promising therapeutic agent in cancer through affecting different molecular targets. Our aim was to demonstrate the molecular machinery of curcumin-mediated apoptosis in autocrine GH + MCF-7, MDA-MB-453 and MDA-MB-231 breast cancer cells (BCCs). Stable GH expressing BCCs were generated by GH gene insert PC3.1 plasmid transfection and Neomycin selection. Although GH + cells are resistant to curcumin treatment, dose-dependent drug exposure decreased cell viability, inhibited colony formation, invasion-metastasis via suppressing GH expression in each BCCs. Anti-hormonal concentration of curcumin (20 µM for MCF-7, MDA-MB-453 and 25 µM for MDA-MB-231) inhibited NF-κB p65 (Ser 536) phosphorylation and decreased DNA binding activity of NF-κB p65 in autocrine GH expressing BCCs. In addition, autocrine GH-mediated IL-1α, IL-6, IL-1β pro-inflammatory cytokine expressions downregulated by curcumin treatment. Moreover, curcumin overcome autocrine GH triggered drug resistant and induced caspase-mediated apoptotic cell death through activating Polyamine (PA) catabolic pathway enzymes which led to generation of toxic by-products such as H2O2 in MCF-7, MDA-MB-453 and MDA-MB-231 GH + BCCs. In conclusion, curcumin could overcome GH-mediated resistant phenotype via modulating NF-κB-mediated inflammatory cytokine expression and PA catabolic machinery activation in breast cancer cells.

Paclitaxel (PTX), cytotoxic agent extracted from Taxus brevifolia has significant antineoplastic activity against breast cancer. Poly d,l-lactide-co-glycolide (PLGA) has been widely used for the preparation of nanoparticles carrying cytotoxic drug agents. The aim of this study was to evaluate the effect of PTX solution and paclitaxel-loaded PLGA nanoparticles (PTX-PLGA-NPs) on MCF-7 cell line. PTX was encapsulated within PLGA nanoparticles by nanoprecipitation method as described by Fessi et al. (1989). Particle size, polydispersity index, zeta potential and encapsulation efficiency of nanoparticles were investigated. Cytotoxic effects of the various concentrations of PTX and PTX-PLGA-NPs on MCF-7 cell line were determined by MTT assay. The cells were treated with various PTX and PTX-PLGA-NPs concentrations (1–10 µg/mL) for 24 h. Particle size, polydispersity index, zeta potential and encapsulation efficiency were found as 267 ± 14 nm, 0.29, −28 ± 3 mV and 76% respectively. According to MTT results, the cytotoxic effect of PTX-PLGA-NPs on MCF-7 cells significantly increased in comparison to PTX solution at all concentrations. This can be attributed to adsorption of PLGA nanoparticles on to the MCF-7 cells to serve a drug reservoir around the cell membrane. It can be concluded that PTX-PLGA-NPs can be promising carriers for anticancer drug delivery.

Abstract: Paclitaxel (PTX) is a cytotoxic agent derived from Taxus brevifolia used for lung cancer. Poly d,l-lactide- co-glycolide (PLGA) is an FDA-approved biodegradable polymer used for preparation of nanoparticles carrying cytotoxic drug agents. The purpose of this study was to evaluate the effect of PTX solution and paclitaxel-loaded PLGA nanoparticles (PTX-PLGA-NPs) on A549 cells. PTX-PLGA-NPs were prepared using nanoprecipation technique as described by Fessi et al. Particle size, polydispersity index, zeta potential and encapsulation efficiency of nanoparticles were measured. Cytotoxic effects of the various concentrations of PTX and PTX-PLGA-NPs on A549 cell line were determined by MTT assay. The cells were treated with various PTX and PTX-PLGA-NPs concentrations (1–10 µg/mL) for 24 h. Particle size, polydispersity index, zeta potential values and encapsulation efficiency were found as 267 ± 14 nm, 0.29, −28 ± 3 mV and 76% respectively. According to MTT results, the cytotoxicity effect of PTX-PLGA-NPs on A549 cells significantly increased in comparison to PTX solution at all concentrations. The enhancement of cytotoxicity can be explained by the sustained release of the PTX from the PLGA nanoparticles and the increase in PTX amount inside the A549 cells. It can be concluded that PTX-PLGA-NPs can be promising systems for anticancer therapy.