RESUMO
Acquired drug resistance constitutes a serious obstacle to the successful therapy of cancer. In the process of therapy resistance, microRNAs can play important roles. In order to combat resistance formation and to improve the efficacy of chemotherapeutics, the mechanisms of the multifaceted hsa-miR-200c on drug resistance were elucidated. Upon knockout of hsa-miR-200c in breast carcinoma cells, a proteomic approach identified altered expression of glutathione S-transferases (GSTs) when cells were treated with the chemotherapeutic drug doxorubicin. In different hsa-miR-200c expression systems, such as knockout, inducible sponge and inducible overexpression, the differential expression of all members of the GST family was evaluated. Expression of hsa-miR-200c in cancer cells led to the repression of a multitude of these GSTs and as consequence, enhanced drug-induced tumor cell death which was evaluated for two chemotherapeutic drugs. Additionally, the influence of hsa-miR-200c on the glutathione pathway, which is part of the phase II detoxification mechanism, was investigated. Finally, the long-term effects of hsa-miR-200c on drug efficacy were studied in vitro and in vivo. Upon doxycycline induction of hsa-miR-200c, MDA-MB 231 xenograft mouse models revealed a strongly reduced tumor growth and an enhanced treatment response to doxorubicin. A combined treatment of these tumors with hsa-miR-200c and doxorubicin resulted in complete regression of the tumor in 60% of the animals. These results identify hsa-miR-200c as an important player regulating the cellular phase II detoxification, thus sensitizing cancer cells not expressing this microRNA to chemotherapeutics and reversing drug resistance through suppression of GSTs.
RESUMO
An amphiphilic core/shell-type polymer-based drug carrier system (HPAE- PCL-b -MPEG), composed of hyperbranched poly(aminoester)-based polymer (HPAE) as the core building block and poly(ethylene glycol)-b - poly(ε-caprolactone) diblock polymers (MPEG-b -PCL) as the shell building block, was designed. The synthesized polymers were characterized with FTIR, 1 H NMR, 13 C NMR, and GPC analysis. Monodisperse HPAE-PCL-b - MPEG nanoparticles with dimensions of < 200 nm and polydispersity index of < 0.5 were prepared by nanoprecipitation method and characterized with SEM, particle size, and zeta potential analysis. 5-Fluorouracil was encapsulated within HPAE-PCL-b -MPEG nanoparticles. In vitro drug release profiles and cytotoxicity of blank and 5-fluorouracil-loaded nanoparticles were examined against the human colon cancer HCT116 cell line. All results suggest that HPAE-PCL-b - MPEG nanoparticles offer an alternative and effective drug nanocarrier system for drug delivery applications.
RESUMO
Reactive oxygen species can bind protein, DNA, lipids, and carbohydrates and thus cause an oxidation reaction that induces various syndromes such as cardiovascular diseases, degenerative disease, and cancer types in the human body. Bioactive compounds, such as PUFA, EPA, DHA, and carotenoids in algae, have a chain ring and protect the tissue from chemical damage and reverse the symptoms of some diseases. Algal bioactives also have various biological properties such as anticoagulants, antiviral, antiangiogenic, antitumor, anti-inflammatory, antioxidant, antiproliferative, and immune modulation properties. This study aimed to show in vitro cytotoxic activity effect of Chlorella protothecoides and Nannochloropsis oculata microalgal extracts loaded nano-microparticles on A-172 (Homo sapiens brain glioblastoma) and HCT-116 (H. sapiens colon colorectal carcinoma) cell lines because of the increasing importance of algal biotechnology. MTT viability tests were performed on HUVEC, A172, and HCT 116 cells with particles obtained at optimum process parameters. The cell viability rates of encapsulated particles were also compared with pure algae extracts. Microalgal extracts loaded nano-micro particles showed very promising results for cytotoxic effect on cancer cells.
