Prodigiosin Concentration Research Articles

Prodigiosin Inhibits Transforming Growth Factor β Signaling by Interfering Receptor Recycling and Subcellular Translocation in Epithelial Cells.

Prodigiosin (PG) is a naturally occurring polypyrrole red pigment produced by numerous microorganisms including some Serratia and Streptomyces strains. PG has exhibited promising anticancer activity; however, the molecular mechanisms of action of PG on malignant cells remain ambiguous. Transforming growth factor-β (TGF-β) is a multifunctional cytokine that governs a wide array of cellular processes in development and tissue homeostasis. Malfunctions of TGF-β signaling are associated with numerous human cancers. Emerging evidence underscores the significance of internalized TGF-β receptors and their intracellular trafficking in initiating signaling cascades. In this study, we identified PG as a potent inhibitor of the TGF-β pathway. PG blocked TGF-β signaling by targeting multiple sites of this pathway, including facilitating the sequestering of TGF-β receptors in the cytoplasm by impeding the recycling of type II TGF-β receptors to the cell surface. Additionally, PG prompts a reduction in the abundance of receptors on the cell surface through the disruption of the receptor glycosylation. In human Caucasian lung carcinoma cells and human hepatocellular cancer cell line cells, nanomolar concentrations of PG substantially diminish TGF-β-triggered phosphorylation of Smad2 protein. This attenuation is further reflected in the suppression of downstream target gene expression, including those encoding fibronectin, plasminogen activator inhibitor-1, and N-cadherin. SIGNIFICANCE STATEMENT: Prodigiosin (PG) emerges from this study as a potent TGF-β pathway inhibitor, disrupting receptor trafficking and glycosylation and reducing TGF-β signaling and downstream gene expression. These findings not only shed light on PG's potential therapeutic role but also present a captivating avenue towards future anti-TGF-β strategies.

Transcriptomic analysis of cell envelope inhibition by prodigiosin in methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading threat to public health as it is resistant to most currently available antibiotics. Prodigiosin is a secondary metabolite of microorganisms with broad-spectrum antibacterial activity. This study identified a significant antibacterial effect of prodigiosin against MRSA with a minimum inhibitory concentration as low as 2.5 mg/L. The results of scanning electron microscopy, crystal violet staining, and confocal laser scanning microscopy indicated that prodigiosin inhibited biofilm formation in S. aureus USA300, while also destroying the structure of the cell wall and cell membrane, which was confirmed by transmission electron microscopy. At a prodigiosin concentration of 1.25 mg/L, biofilm formation was inhibited by 76.24%, while 2.5 mg/L prodigiosin significantly reduced the vitality of MRSA cells in the biofilm. Furthermore, the transcriptomic results obtained at 1/8 MIC of prodigiosin indicated that 235and 387 genes of S. aureus USA300 were significantly up- and downregulated, respectively. The downregulated genes were related to two-component systems, including the transcriptional regulator LytS, quorum sensing histidine kinases SrrB, NreA and NreB, peptidoglycan biosynthesis enzymes (MurQ and GlmU), iron-sulfur cluster repair protein ScdA, microbial surface components recognizing adaptive matrix molecules, as well as the key arginine synthesis enzymes ArcC and ArgF. The upregulated genes were mainly related to cell wall biosynthesis, as well as two-component systems including vancomycin resistance-associated regulator, lipoteichoic acid biosynthesis related proteins DltD and DltB, as well as the 9 capsular polysaccharide biosynthesis proteins. This study elucidated the molecular mechanisms through which prodigiosin affects the cell envelope of MRSA from the perspectives of cell wall synthesis, cell membrane and biofilm formation, providing new potential targets for the development of antimicrobials for the treatment of MRSA.

Biosynthesis of Nio Nanoparticles Using Prodigiosin Pigment and its Evaluate of Antibacterial Activity Against Biofilm Producing MDR- Pseudomonas Aeruginosa

The entire investigation's focus was on the production of nickel oxide nanoparticles (NiONPs), using prodigiosin pigments produced by Serratia marcescens as a stabilizing and reducing agent. Nickel oxide nanoparticles are synthesized using nickel sulfate NiSO4 (10mg) with a concentration of prodigiosin (10g/100ml). Biosynthesized NiO nanoparticles have been characterized by using many techniques, such as (UV-Vis, AFM, XRD, FTIR, and FE-SEM). The AFM analysis revealed that NiONPs have an average diameter size of (41.77 mm), and the FE-SEM Image displays Spherical. Additionally, the effect of NiONPs with different concentrations on the bacteria Pseudomonas aeruginosa was measured and the inhibition zone reached to (29 mm). Biosynthesis of NiONPs using prodigiosin was shown to have promising activity as an antibacterial against the biofilm-producing Pseudomonas aeruginosa.

The effectiveness of antimicrobial photodynamic therapy with prodigiosin against reference strains of Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

Prodigiosin (PG) is a secondary metabolite of bacterial origin that is able to absorb the visible light and plays a role as a photosensitizer in photodynamic therapy (PDT). This in vitro study aimed to investigate the cytotoxicity of PG-mediated PDT against the reference strains of Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PG were determined. Each strain was then allocated into four groups as follows: G1: control (no treatment), G2: PG-treated groups that received different PG concentrations (1000-1.95μM), G3: laser-treated group (wavelength: 520nm, radiation dose: 187J/cm2), and G4: PG-mediated PDT groups that were initially treated with different concentrations of PG and were then exposed to laser irradiation in the same way as the previous group. Finally, the number of colony-forming units per milliliter (CFU/mL) was calculated and analyzed using the SPSS software. PG had both bacteriostatic and bactericidal activities on the tested bacteria, with the maximum antibacterial effect being observed against S. aureus. In all bacterial strains, the maximum number of CFUs was observed in the control group followed by the laser-irradiated and PG-treated groups, but the differences were not statistically significant (p > 0.05). However, the utilization of PG-mediated PDT resulted in a significant decrease in the mean number of CFUs in all the tested bacteria (p < 0.0001). PG-mediated PDT had the potential to kill some bacterial strains in the laboratory. Yet, further studies are warranted to confirm its efficacy and safety to be applied in clinical settings.

An in-situ approach based in mineral oil to decrease end-product inhibition in prodigiosin production by Serratia marcescens

Prodigiosin is an intense red microbial pigment produced by Serratia marcescens strains. Although various in-vitro activities make it attractive for the pharmaceutical and food industry, the production of this alkaloid is dramatically affected by media components and feedback inhibition, resulting in low productivities and high commercial costs. The present work proposes an interest low-cost production coupled to a two-phase in-situ product recovery system based on mineral oil to improve prodigiosin production. The scale-up of this strategy at batch and continuous processes was also studied. A medium composed of peanut (40 g/L) and defatted soybean flour (5.25 g/L) resulted in the highest prodigiosin titers. The addition of mineral oil (5 % v/v) triggered a 1.12-fold and 2-fold at pigment content and cell density, respectively. Scale-up at batch bioreactor resulted in a prodigiosin concentration of 1282 mg/L. However, continuous fermentation reached a 1.5-fold in the production rate compared to batch. Mathematical modeling was used to describe batch process behavior, obtaining all R2 above 0.975. From these results, a potential large-scale strategy could be proposed for an industrially attractive prodigiosin production system using S. marcescens via fermentation, alleviating end-product inhibition phenomenon and putting it in perspective with an economical approach.

Downstream Process Development for Extraction of Prodigiosin: Statistical Optimization, Kinetics, and Biochemical Characterization

Prodigiosin is natural red colourant derived from Serratia marcescens. However, the high cost of prodigiosin restricts its use in food and pharmaceutical industries, which can be addressed with the design of a suitable extraction procedure. Therefore, the present study aims to use Taguchi methodology to optimize various process parameters during ultrasound-assisted extraction (UAE) to get a higher prodigiosin extraction yield. The most significant contribution comes from the solid-to-liquid ratio (36.66%), followed by sonication of duty cycle (34.82%), medium pH (15.7%), and acoustic intensity (12.82%). The Taguchi technique predicts the highest optimal yield using the solid-liquid ratio (0.3g/mL), duty cycle sonication (75%), acoustic intensity (12.5 w/cm2), and medium pH (3) as parameters. When the extraction conditions were optimized, the yield of prodigiosin increased by 4166.89mg/L. In the future, the above extraction conditions determined using Taguchi approach will be applied for large-scale extraction of prodigiosin. Finally, a second-order kinetic model is used to suit the batch extraction investigation and the second-order rate constant (k) has a value of 4 × 10-5 L/mg/min. In the future, the rate constant, which is reported for the first time, will be used to create a batch extractor for commercial extraction of prodigiosin. Prodigiosin has also been shown to have substantial antioxidant and scavenging properties, which increase in a dose-dependent way with prodigiosin concentration. Because of its antioxidant and scavenging properties, prodigiosin can be used as food additives or pharmaceutical ingredients in industries.

EVALUATION OF THE BIOLOGICAL EFFECT SYNTHESIZED IRON OXIDE NANOPARTICLES ON ENTEROCOCCUS FAECALIS

This study was aimed to demonstrate the biosynthesis procedure of iron oxide nanoparticles (Fe2O3 NPs) by using prodigiosin pigment produced from environmental isolate Serratia marcescens as a reducing and stabilizing agent. Additionally, the synthesis conditions were precisely taken into consideration as a pH of 7 and a temperature of 50°C alongside a concentration of prodigiosin of 12 mg/ml with a precursor of ferric sulfate of 5 mg/50ml in deionized distilled water (DDW). Biosynthesized Fe2O3 nanoparticles have presented many applications such as catalysis, biosensing, anticancer, and biomedical, etc. The study of optimum condition for the synthesis of Fe2O3 was characterized by different techniques, such as (XRD, UV-VIS, AFM, FTIR and FE-SEM). The wavelength of biosynthesis of Fe2O3 by using UV-VIS is (284 nm), Image FE-SEM displays Spherical Fe2O3 NPs in nano-cluster form and the average volume is (35.01) nm). And the effect of Fe2O3 NPs on bacteria Enterococcus faecalis on an inhibition zone 31 mm.

Optimized prodigiosin production with Pseudomonas putida KT2440 using parallelized noninvasive online monitoring.

The red pigment prodigiosin is of high pharmaceutical interest, due to its potential applications as an antitumor drug and antibiotic agent. As previously demonstrated, Pseudomonas putida KT2440 is a suitable host for prodigiosin production, as it exhibits high tolerance toward the antimicrobial properties of prodigiosin. So far, prodigiosin concentrations of up to 94 mg/L have been achieved in shake flask cultivations. For the characterization and optimization of the prodigiosin production process, the scattered light of P. putida and fluorescence of prodigiosin was measured. The excitation and emission wavelengths for prodigiosin measurement were analyzed by recording 2D fluorescence spectra. The strongest prodigiosin fluorescence was obtained at a wavelength combination of 535/560 nm. By reducing the temperature to 18 °C and using 16 g/L glucose, the prodigiosin concentration was more than doubled compared with the initial cultivation conditions. The obtained results demonstrate the capabilities of parallelized microscale cultivations combined with noninvasive online monitoring of fluorescence for rapid bioprocess development, using prodigiosin as a molecule of current biotechnological interest.

EVALUATION OF THE BIOLOGICAL EFFECT SYNTHESIZED ZINC OXIDE NANOPARTICLES ON PSEUDOMONAS AERUGINOSA

This study was aimed to demonstrate the biosynthesis procedure of Zinc oxide nanoparticles (ZnO NPs) using Prodigiosin pigment which in turn produced from particular environmental bacteria isolates Serratiamarcescensas a stabilizing and reducing agent. Additionally, the synthesis conditions were precisely taken into consideration as a pH of 7 and a temperature of 50°C alongside a concentration of prodigiosin of 12 mg/ml with 5mg precursor of zinc acetate in deionized distilled water (DDW) 50ml. Biosynthesized ZnO nanoparticles have presented many applications such as catalysis, biosensing, anticancer, and biomedical, etc. The optimum condition for ZnO biosynthesis was characterized through several techniques such as UV-Vis, AFM, XRD, FT-IR, and FE-SEM. In particular, a cut-off phenomenon of the biological synthesized ZnO was found at around 280 nmusing UV-Vis, while spherical shape particles were noticed using FE-SEM techniques. Also, the AFM analysis revealed that ZnO NPs an average diameter size of 45.02 nm.And the effect of ZnO NPs on bacteriaPseudomonas aeruginosaon an inhibition zone 29mm.

Prodigiosin Production and Photoprotective/Antigenotoxic Properties in Serratia marcescens Indigenous Strains from Eastern Cordillera of Colombia.

Serratia marcescens is a bacterial species that produces an antibacterial pigment (Prodigiosin) showing a wide adaptive response to environmental stresses. The study aimed to investigate Prodigiosin production in S. marcescens wild-type strains, as well as its relation to photoprotection and antigenotoxicity against UVB. Prodigiosin yield was spectrophotometrically assayed in extracts of bacterial strains grown in different culture media. In vitro photoprotection efficacy was evaluated using the invitro indices sun protection factor (SPFinvitro ) and critical wavelength (λc). The percentage of UVB antigenotoxicity estimates (%GI) in the SOS Chromotest was also evaluated. Correlation analysis was used to examine the relationship between Prodigiosin yield, SPFinvitro , %GI estimates and environmental traits (altitude, temperature, rainfall and solar irradiance). Prodigiosin yield in S. marcescens strains varied depending on culture media used for its growth, and it was correlated with environmental variables such as temperature and solar irradiance. SPFinvitro estimates were well correlated with Prodigiosin concentration and %GI values in the bacterial strains being studied. UVB photoprotective efficacy of the extracts obtained from S. marcescens strains depends on the strain's Prodigiosin yield and its antigenotoxic potential. The extracts with Prodigiosin yield higher than ~17 μg mL-1 could be used as sources of sunscreen ingredients.

Statistical Optimization of Prodigiosin Production by Plackett-burman Design for Bacteria Isolated from Indian Marine Soil

The current investigation was conducted to maximise the production of the natural anticancer drug from the microbe isolated from the marine soil sample of the Coromandel Coast of the Bay of Bengal region of India. Yellow to red colour pigmented microbes separated by crowd plate method. Bacteria are producing strong colour product subjected to future study. The isolated strains were detected based on biochemical, morphological, and genetic characteristics. Pigment formation was found to be influenced strongly by conditions of the environment. The water-insoluble pigment extracted by acidified methanol and showed maximum absorbance at 535nm. A statistical screening procedure was adopted to select the optimum condition to produce the pigment. The carbon, nitrogen, medium pH, growth condition temperature and revolution of agitation were screened using the response surface methodology statistical model. The near optimum conditions for the production medium were affected by the concentration of peanut, L-proline, percentage inoculum pH and incubation time. When these conditions were employed yield increased as two-fold as the concentration of prodigiosin 789 mg/l.

Synthesis and Characterization of Silver Nanoparticles Using Prodigiosin Pigment and Evaluation of Their Antibacterial and Anti-Inflammatory Activities

This study focused on the biological synthesis of silver nanoparticles (AgNPs), using prodigiosin pigment produced by Serratia marcescens. The effect of parameters such as pH, temperature, time, with various concentrations of silver nitrate (AgNO3) and prodigiosin on the synthesis of AgNPs were also studied. Optimized results of the biosynthesis process revealed an increase in the intensity of Surface Plasmon Resonance (SPR) bands of nanoparticles with shifting at the wavelength of 400 nm. In addition, optimum synthesis of AgNPs was achieved at pH 12, temperature 55℃, and reaction time 24 h, with concentrations of prodigiosin, as a reducing agent, of 12.5 µg/ml and silver ion concentration of 1 mM. Measurement of the size of silver nanoparticles by SEM diffraction revealed a value of 30 nm. Finally, the minimum inhibitory concentration of AgNPs against pathogenic bacteria was 32 µg/ml for Staphylococcus aureus and Pseudomonas aeruginosa. The results of anti-inflammatory effects of Ag NPs obviously demonstrated that the infections of test animals treated with AgNPs were completely healed after 4 days of treatment, while the animals treated with fucidin (as control) did not exhibit any healing.

EVALUATION THE EFFECT OF GREEN SYNTHESIS TITANIUM DIOXIDE NANOPARTICLES ON ACINETOBACTER BAUMANNII ISOLATES

Acinetobacter baumannii is gram negative opportunistic coccobacilli,the most important agent in nosocomial infections with high mortality rate. This bacteria is characterized by (biochemical tests, polymerase chain reaction (PCR) and vitek-2 system). The antibiotic susceptibility result of A. baumannii isolates were shown resistant to (Methicillin, Nitrofurantion), while sensitive to (colistin, Ciprofloxacin).This study was aimed to biosynthesis of titanium dioxide nanoparticles by using prodigiosin pigment produced from clinical isolate Serratia marcescens as reducing and stabilizing agent for Titanium dioxide nanoparticles (TiO2 NPs) and used as antibacterial agent for Acinetobacter baumannii isolated from different clinical sources. TiO2 NPs synthesized by using titanium chloride TiCl4 (5 ml/50 ml) in deionized water with concentration of prodigiosin (10 mg/ml)and adjusted pH at 7 and the temperature at 50 ˚C. TiO2NPs synthesized was Characterized by various technique, such as (AFM , UV-VIS, FTIR , XRD and FE-SEM ). The result showed that wavelength(366)nm was optimum for TiO2NPs that have crystalline shape at average volume (47.52 nm). Green synthesized TiO2 NPs have shown several applications such as biomedical, anticancer, bio sensing, catalysis etc.

Loss of Serine-Type D-Ala-D-Ala Carboxypeptidase DacA Enhances Prodigiosin Production in Serratia marcescens.

Serratia marcescens, a gram-negative bacterium, found in a wide range of ecological niches can produce several high-value products, including prodigiosin, althiomycin, and serratamolide. Among them, prodigiosin has attracted attention due to its immunosuppressive, antimicrobial, and anticancer properties. However, the regulatory mechanisms behind prodigiosin synthesis in Serratia marcescens remains limited. Here, a transposon mutant library was constructed to identify the genes related to prodigiosin synthesis, and BVG90_02415 gene encoding a peptidoglycan synthesizing enzyme D-Ala-D-Ala carboxypeptidase DacA was found to negatively regulates prodigiosin synthesis. Quantitative measurements revealed that disruption of dacA increased prodigiosin production 1.46-fold that of the wild-type strain JNB5-1 in fermentation medium. By comparing differences in cell growth, pigA gene expression level, cell morphology, membrane permeability, and intracellular prodigiosin concentration between wild-type strain JNB5-1 and dacA mutant SK4-72, results revealed that the mechanism for hyper-producing of prodigiosin by the dacA mutant was probably that dacA disruption enhanced prodigiosin leakage, which in turn alleviated feedback inhibition of prodigiosin and increased expression of pig gene cluster. Collectively, this work provides a novel insight into regulatory mechanisms of prodigiosin synthesis and uncovers new roles of DacA protein in regulating cell growth, cell morphology, and membrane permeability in Serratia marcescens. Finally, this study offers a new strategy for improving production of high-value compounds in Serratia marcescens.

Production of a prodigious drug with anticancer and immunosuppressive properties

Prodigiosin is a tripyrrolic pigment that exhibited numerous biological activities including antibacterial, immunosuppressive and anticancer properties. Prodigiosin is reported to kill cancer cell lineages by either inducing caspases dependent apoptosis, DNA intercalation, altering cell signaling pathways or inhibiting the action of topoisomerase I/II. It has been showed cytotoxic effects on hepatocellular carcinoma cells, breast cancer cells and neuroblastoma cells. The present study was aimed at production of prodigiosin and exploring its applications. Peptone glycerol medium (PGM) was used to screen out red colony forming bacteria from waste coconut sample. Pigment production medium was used for production of Prodigiosin. Bacterial culture inoculated in sterile production medium and incubated at 28 ± 2°C at 300 rpm. After incubation cell pellets were harvested and lysed by acidified methanol. Prodigiosin production was confirmed by taking absorbance at 535 nm and by HPLC. On the basis of biochemical tests isolated bacteria was Serratia spp. Nutrient broth did not show accumulation of red pigment in bacterial cells but pigment production medium did. In initial experiments, maximum concentration of prodigiosin synthesized by was 2 g L-1 in pigment production medium. It also exhibited antibacterial activirty against E.coli and Bacillus subtilis. Serratia spp. and pigment production medium could be optimized for a cost effective production of this anticancer drug. The Admet properties for in-silico analysis are under process.

Using prodigiosin against some gram-positive and gram-negative bacteria and Trypanosoma cruzi.

Background:This work aimed to explore the action of natural prodigiosin on both bacterial organisms and Trypanosoma cruzi cells.Methods:Natural prodigiosin pigment was extracted and purified from cultures of Serratia marcescens. Two media, peanut broth and peptone glycerol broth, both recommended in the literature for prodigiosin production, were compared. The prodigiosin obtained was employed to explore its antimicrobial properties against both bacteria and Trypanosoma cruzi cells. Results:Peanut broth yielded four times more prodigiosin. The prodigiosin showed remarkable activity (minimal inhibitory concentrations in the range of 2-8 µM for bacteria and half maximal inhibitory concentration of 0.6 µM for Trypanosoma cruzi). In fact, the prodigiosin concentration required to inhibit parasite growth was as low as 0.25 mg/l versus 4.9 mg/l of benznidazole required. Furthermore, atomic force microscopy revealed marked morphological alterations in treated epimastigote forms, although no pore-formation activity was detected in protein-free environments. Conclusions:This work demonstrates the potential usefulness of prodigiosin against some gram-positive and gram-negative bacteria and Trypanosoma cruzi although further studies must be done in order to assess its value as a candidate molecule.

Classical and Statistical Optimization of Medium Composition for Promoting Prodigiosin Produced by Local Isolate of Serratia Marcescens

Prodigiosin is a ‘natural red pigment produced by Serratia marcescens which exhibits immunosuppressive and anticancer properties in addition to antimicrobial activities. This work presents an attempt to maximize the production of prodigiosin by two different strategies: one factor at time (OFAT) and statistical optimization. The result of OFAT revealed that sucrose and peptone were the best carbon and nitrogen sources for pigment production with concentration of prodigiosin of about 135 mg/ L. This value was increased to 331.6mg/ L with an optimized ratio of C/N (60:40) and reached 356.8 with pH 6 and 2% inoculum size at end of classical optimization. Statistical experimental design based on Response surface methodology was conducted to optimize the composition of trace element. The design revealed that the predicted prodigiosin production of 406 mg/L can be achieved when concentrations of trace element CaCl2·2H2O, FeSO4·4H2O, MgSO4·7H2O and MnSO4·4H2O were equal to 9.22, 0.32, 0.67 and 2.48 g/L, respectively. The actual production of prodigiosin in the optimized medium was 375 mg/L. Growth kinetics of S. marcescens were evaluated in optimized medium which revealed that prodigiosin was ‘non-associated growth’ secondary metabolite with maximum production of approximately 365.7 mg/L obtained after 54 hours of incubation.&#x0D;

Antiproliferative, antioxidant and binding mechanism analysis of prodigiosin from newly isolated radio-resistant Streptomyces sp. strain WMA-LM31.

Streptomyces genus are filamentous Gram positive bacteria, of great intrest, producing biologically active compounds. Recent market and consumer curiosity in natural products have forced scientist and industry for the development of new products with therapeutic potential. This study focuses on evaluation of antioxidant and anticancerous properties of prodigiosin from radio-resistant Streptomyces sp. strain WMA-LM31. A molecular docking approach was adopted to understand theoretical binding mechanism and affinity for anticancer targets. A radio-resistant bacterium, labelled as strain WMA-LM31, was isolated from desert soil and screened for its radio-resistant potential and prodigiosin production. 16S rRNA gene sequencing showed that the bacterium clusters to genus Streptomyces and found resistant to ultraviolet radiation (dosage of 2 × 103J/m2). Strain WMA-LM31 produced a red color pigment in tryptone glucose yeast (TGY) medium.The LC-MS analysis of the purified compound showed a molar mass of 324 [m/z]+ matched the chemical formula C20H25N3O, identified as prodigiosin. The compound showed strong antioxidant (62.51%) activities along with significant inhibitory action against oxidative damages to bovine serum albumin (BSA) and mice liver lipids in comparison to standard ascorbic acid. IC50 values of HepG2 and HeLa cell lines was found at 12.66 and 14.83µg/mL of prodigiosin concentration, respectively. Furthermore, molecular docking was performed with two different cancers macromolecular targets: [2O2F (Bcl-2) and 1DI8 (CDK-2)], and BSA (PDB id: 3V03). The results indicated that the binding affinity of prodigiosin to its target molecules is due to the presence of terminal pyrrole rings. It is concluded from the results that prodigiosin from Streptomyces sp. strain WMA-LM31 has strong antioxidant, anticancer and apoptotic properties. The knowledge of binding mechanisms and interactions of prodigiosin could provide future directions in designing potent target specifc drugs.

Prodigiosin produced by Serratia marcescens inhibits expression of MMP-9 and survivin and promotes caspase-3 activation with induction of apoptosis in acute lymphoblastic leukaemia cells.

Matrix metalloproteinase-9 (MMP-9) and survivin are involved in several steps of carcinogenesis in acute lymphoblastic leukaemia (ALL). Yet, no MMP-9 and survivin-modulating drugs with low toxicity on normal cells but high efficacy against high MMP-9- and survivin-expressing leukaemia cells have been approved for clinical application in ALL. Prodigiosin, a secondary metabolite of Serratia marcescens, induces apoptosis in different kinds of cancer cells with low toxicity on normal cells. However, little is known about the effects of this compound on the high MMP-9- and survivin-expressing leukaemia cells. CCRF-CEM cells as a model for high MMP-9- and survivin-expressing ALL cells were treated with 100, 200 and 400nmoll-1 prodigiosin after which cell number, proliferation rate, MMP-9 and survivin expression, caspase-3 activation and apoptosis were evaluated. After 24-, 48-, and 72-h treatments with 100, 200 and 400nmoll-1 prodigiosin, proliferation rates were measured to be 92·3-76·7%, 82-63% and 63·7-46·6% respectively. Treatment with prodigiosin for 48h decreased MMP-9 mRNA levels followed by decreases in secreted (S) and intracellular (I) MMP-9 protein levels by 20-22% and 69-72% for 100-400nmoll-1 prodigiosin respectively. Prodigiosin decreased survivin protein levels from 40 to 26% followed by 3·7-5·6-fold increases in caspase-3 activation for the aforementioned prodigiosin concentration ranges. Treatment with 100-400nmoll-1 prodigiosin increased the caspase-3/survivin, caspase-3/I-MMP-9 and caspase-3/S-MMP-9 ratios by 6-7·3-, 11·5-19·1- and 4·9-6·8-fold increases respectively. A dramatic increase in the number of apoptotic cells was also observed with increasing prodigiosin concentrations. The inhibitory effects of prodigiosin on MMP-9 and survivin expression, as well as its pro-apoptotic capacity, represent a novel therapeutic avenue against ALL cells. These findings provide an important and interesting basis to develop a new therapeutic compound with high potential against ALL cells.

Real-Time Recording of the Cellular Effects of the Anion Transporter Prodigiosin

Summary The unraveling of the cellular effects of anion transporters is key to their potential development as apoptosis-inducing or autophagy-disrupting therapeutics. Here, we conducted a systematic study of the cellular responses to the anion transporter prodigiosin by using a pH on/off responsive near-infrared (NIR)-fluorescent probe in HeLa and LAMP1-GFP-transfected HeLa cell lines. The sequence of localized and global cellular acidity changes and the resulting outcomes induced by the anion transporter were visualized with high temporal and spatial resolution. The results show that prodigiosin causes the pH within the lysosomal lumen to rise, after which a non-organelle-specific increase in acidity of the cytosol takes place, which prompts cells to undergo apoptosis. This was confirmed by the quantification of NIR-emissive lysosomes, the intra-cellular fluorescence intensity, and fluorescence volume over time. This NIR probe overcame the limitations of acridine orange, which to date have severely restricted researchers in this field.