Glioblastoma multiforme (GBM) cells are characterised by their extreme chemoresistance. The activity of multiple-drug resistance (MDR) transporters that extrude antitumor drugs from cells plays the most important role in this phenomenon. To date, the mechanism controlling the expression and activity of MDR transporters is poorly understood. Activity of the enzyme ecto-5 0 -nucleotidase (CD73) in tumor cells, which hydrolyses AMP to adenosine, has been linked to immunosuppression and prometastatic effects in breast cancer and to the proliferation of glioma cells. In this study, we identify a high expression of CD73 in surgically resected samples of human GBM. In primary cultures of GBM, inhibition of CD73 activity or knocking down its expression by siRNA reversed the MDR phenotype and cell viability was decreased up to 60% on exposure to the antitumoral drug vincristine. This GBM chemosensitization was caused by a decrease in the expression and activity of the multiple drug associated protein 1 (Mrp1), the most important transporter conferring multiple drug resistance in these cells. Using pharmacological modulators, we have recognized the adenosine A 3 receptor subtype in mediation of the chemoresistant phenotype in these cells. In conclusion, we have determined that the activity of CD73 to trigger adenosine signaling sustains chemoresistant phenotype in GBM cells. ORIGINAL RESEARCH ARTICLE 602 J o u r n a l o f J o u r n a l o f Cellular Physiology Cellular Physiology ß 2 0 1 2 W I L E Y P E R I O D I C A L S , I N C .
Microcins are low-molecular-weight proteins secreted by certain bacteria that act by limiting the growth of other bacteria that share the same ecological niche. In the present work, the previous microcin 24 system was resequenced.We detected three nucleotide differences in the microcin-coding gene that partially change the amino acid sequence. According to the present microcin nomenclature, we renamed the five genes constituting this microcin system (mcnRINAB), which are arranged in an operon-like structure: mcnR codes for a putative histone-like nucleoid protein regulator; mcnI codes for the immunity protein; mcnN encodes microcin N; and mcnA and mcnB correspond to an ATP-binding cassette transporter system. Purified microcin N has a molecular weight of 7274.23 Da, as determined by MS. This peptide was stable up to 100°C, resistant to treatment with lipase, lysozyme, trypsin, and chymotrypsin, and susceptible to degradation by proteinase K.
Cryptocarya alba (Peumo; CA) and Laurelia sempervirens (Laurel; LS) are herbs native to the Chilean highlands and have historically been used for medicinal purposes by the Huilliches people. In this work, the essential oils were extracted using hydrodistillation in Clevenger apparatus and analyzed by GC-MS to determine their composition. The antioxidant capacity (AC) was evaluated in vitro. The cytotoxicity was determined using cell line cultures both non tumoral and tumoral. The toxicity was determined using the nematode Caenorhabditis elegans. The antimicrobial activity was evaluated against 52 bacteria using the agar disc diffusion method and the minimum inhibitory concentrations (MICs) were determined. The principal compounds found in C. alba essential oil (CA_EO) were α-terpineol (24.96%) and eucalyptol (21.63%) and were isazafrol (91.9%) in L. sempervirens essential oil (LS_EO). Both EOs showed antioxidant capacity in vitro. Both EO showed antibacterial activity against bacteria using. LS_EO showed more inhibitory effect on these cell lines respect to CA_EO. Both EOs showed toxicity against the nematode C.elegans at 3.12–50 mg/mL. The essential oils of CA and LS have an important bioactive potential in their antioxidant, antibacterial and cytotoxicity activity. Both essential oils could possibly be used in the field of natural medicine, natural food preservation, cosmetics, sanitation and plaguicides among others.
The findings of this study underscore the need to improve patient-physician communication during chemotherapy to reduce the symptom burden among Hispanic breast cancer patients.
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