ABSTRACT
PURPOSE: This study aimed to investigate whether Mullerian inhibiting substance (MIS) in combination with calcitriol modulates proliferation and apoptosis of human ovarian cancer (OCa) cell lines (SKOV3, OVCAR3, and OVCA433) and identify the signaling pathway by which MIS mediates apoptosis. MATERIALS AND METHODS: OCa cell lines were treated with MIS in the absence or presence of calcitriol. Cell viability and proliferation were evaluated using the Cell Counting Kit-8 assay and apoptosis was evaluated by DNA fragmentation assay. Western blot and enzyme-linked immunosorbent assay were used to determine the signaling pathway. RESULTS: The cells showed specific staining for the MIS type II receptor. Treatment of OCa cells with MIS and calcitriol led to dose- and time-dependent inhibition of cell growth and survival. The combination treatment significantly suppressed cell growth, down-regulated the expression of B-cell lymphoma 2 (Bcl-2), and up-regulated the expressions of Bcl-2 associated X protein, caspase-3, and caspase-9 through the extracellular signal-regulated kinase signaling pathway. CONCLUSION: These results, coupled with a much-needed decrease in the toxic side effects of currently employed therapeutic agents, provide a strong rationale for testing the therapeutic potential of MIS, alone or in combination with calcitriol, in the treatment of OCa.
Subject(s)
Female , Humans , Anti-Mullerian Hormone/pharmacology , Apoptosis/drug effects , Calcitriol/pharmacology , Caspase 3/metabolism , Caspase 9/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Fragmentation/drug effects , Enzyme-Linked Immunosorbent Assay , Extracellular Signal-Regulated MAP Kinases/metabolism , Growth Inhibitors/metabolism , Ovarian Neoplasms/drug therapy , Receptors, Peptide , Receptors, Transforming Growth Factor beta , Signal Transduction/drug effectsABSTRACT
The aim of this study was to evaluate the growth of the B. abortus reference strains and field isolates on media containing different inhibitor agents. Reference strains were seeded on tryptose agar containing: i-erythritol (1.0 mg/mL), fuchsin (20 μg/mL and 80 μg/mL), thionin (2.5 μg/mL and 10 μg/mL), rifampicin (200 μg/mL) and safranin O (200 μg/mL). Field isolates were tested only on media containing i-erythritol, rifampicin and thionin. Furthermore, each suspension was also inoculated on tryptose agar incubated in air, to test its ability to grow without CO2. Sensitivity to fuchsin was similar among reference strains evaluated. Growth of S19, 544 and 2308 but not RB51 were inhibited on media containing rifampicin. Medium with safranin O showed no inhibition for RB51, 544 and 2308, but it partially inhibited the S19 growth as well as medium containing i-erythritol. Treatment/control growth ratio for 2308 on tryptose agar containing thionin (2.5 μg/mL) was approximatelly 1.0, whereas S19 and RB51 showed 0.85 and 0.89 ratios, respectively. Growth of 544, S19 and RB51 but not 2308 was completely inhibited on medium with thionin (10 μg/mL). All field strains grew on medium containing i-erythritol, but were completelly inhibited by rifampicin. With exception of A1 (B. abortus biovar 3) all field isolates grew on medium with thionin, although some strains showed a treatment/control growth ratio of 0.75–0.80 (10 μg/mL). These results showed that tryptose agar with thionin, i-erythritol or rifampicin could be useful for differentiating vaccine, challenge and field strains of B. abortus.
Subject(s)
Animals , Humans , Bacteriological Techniques/methods , Brucella abortus/drug effects , Brucella abortus/growth & development , Culture Media/chemistry , Growth Inhibitors/metabolism , Brucella abortus/classification , Brucella abortus/isolation & purificationABSTRACT
Fungi have been recently recognized as organisms able to grow in presence of high salt concentration with halophilic and halotolerance properties and their ligninolytic enzyme complex have an unspecific action enabling their use to degradation of a number of xenobiotic compounds. In this work, both the effect of salt and polyols on growth of the basidiomycetes strains, on their ability to produce ligninolytic enzyme and diuron degradation were evaluated. Results showed that the presence of NaCl in the culture medium affected fungal specimens in different ways. Seven out of ten tested strains had growth inhibited by salt while Dacryopinax elegans SXS323, Polyporus sp MCA128 and Datronia stereoides MCA167 fungi exhibited higher biomass production in medium containing 0.5 and 0.6 mol.L-1 of NaCl, suggesting to be halotolerant. Polyols such as glycerol and mannitol added into the culture media improved the biomass and ligninases production by D. elegans but the fungus did not reveal consumption of these polyols from media. This fungus degraded diuron in medium control, in presence of NaCl as well as polyols, produced MnP, LiP and laccase.
Subject(s)
Basidiomycota/enzymology , Basidiomycota/metabolism , Herbicides/metabolism , Oxygenases/metabolism , Sodium Chloride/metabolism , Biomass , Biotransformation , Basidiomycota/drug effects , Basidiomycota/growth & development , Culture Media/chemistry , Diuron/metabolism , Growth Inhibitors/metabolism , Growth Inhibitors/toxicity , Polymers/metabolism , Polymers/toxicity , Sodium Chloride/toxicityABSTRACT
Serum protease inhibitors were determined in paired sera from 7 patients with cerebral malaria and 2 patients with acute malaria showing high and low growth inhibition activity in the initial and follow-up sera respectively. Alpha-1 antichymotrypsin and alpha-1 antitrypsin but not alpha-2 macroglobulin showed direct correlation with the growth inhibition activity. When alpha-1 antitrypsin was deliberately added to the malarial culture no growth inhibition occurred indicating that the alpha-1 antichymotrypsin was the most likely factor responsible for inhibition of growth of malarial parasites in vitro.