Prodigiosin/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights

Anwar, Mohammed Moustapha; Shalaby, Manal; Embaby, Amira M.; Saeed, Hesham; Agwa, Mona M.; Hussein, Ahmed

doi:10.1038/s41598-020-71157-w

Cited by 38 publications

(38 citation statements)

References 125 publications

(193 reference statements)

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“…In the present study, the co-delivery of SIM and PG based on a targeting nanocarrier platform was considered and investigated on cell line culture systems. The PG compound was introduced as a proapoptotic ligand via cleavage of double stranded DNA and disruption of the pH gradient ( Pérez-Tomás and Vinas, 2010 ; Anwar et al, 2020 ). According to our results, the present co-drug delivery formulation showed a stronger cytotoxic effect than the nanoparticles loaded with only one drug (PG or SIM) or the free drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Prodigiosin (PG) is a red pigment from Serratia marcescens ( Rastegari and Karbalaei-Heidari, 2016 ), that exhibits anticancer activity in eukaryotic cells due to its proapoptotic action, cleavage of double stranded DNA and disruption of the pH gradient ( Pérez-Tomás and Vinas, 2010 ; Anwar et al, 2020 ). On the other hand, cholesterol is an essential component of the cellular membrane, it accumulates in cancer cells and tumor tissues and is involved in various cellular processes such as cell growth, proliferation, and migration.…”

Section: Introductionmentioning

confidence: 99%

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Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Mirzaeinia

Zeinali

Budiša

et al. 2022

Front. Bioeng. Biotechnol.

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Biological metal-organic frameworks (BioMOFs) are hybrid compounds in which metal nodes are linked to biocompatible organic ligands and have potential for medical application. Herein, we developed a novel BioMOF modified with an anti-VEGFR1 scFv antibody (D16F7 scFv). Our BioMOF is co-loaded with a combination of an anticancer compound and a lipid-lowering drug to simultaneously suppress the proliferation, growth rate and metastases of cancer cells in cell culture model system. In particular, Prodigiosin (PG) and Simvastatin (SIM) were co-loaded into the newly synthesized Ca-Gly BioMOF nanoparticles coated with maltose and functionalized with a recombinant maltose binding protein-scFv fragment of anti-VEGFR1 (Ca-Gly-Maltose-D16F7). The nanoformulation, termed PG + SIM-NP-D16F7, has been shown to have strong active targeting behavior towards VEGFR1-overexpresing cancer cells. Moreover, the co-delivery of PG and SIM not only effectively inhibits the proliferation of cancer cells, but also prevents their invasion and metastasis. The PG + SIM-NP-D16F7 nanocarrier exhibited stronger cytotoxic and anti-metastatic effects compared to mono-treatment of free drugs and drug-loaded nanoparticles. Smart co-delivery of PG and SIM on BioMOF nanoparticles had synergistic effects on growth inhibition and prevented cancer cell metastasis. The present nanoplatform can be introduced as a promising tool for chemotherapy compared with mono-treatment and/or non-targeted formulations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Mirzaeinia

Zeinali

Budiša

et al. 2022

Front. Bioeng. Biotechnol.

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“…Recently, the study of PG has been renewed and increased due to its beneficial effects, especially its high anticancer activity [11,13] and lack of toxicity to normal cells [11]. To enhance the anticancer effect, PG was combined with other agents [14], formed nanoparticle sizes [15], and synthesized its derivatives [16]. Thus, the large-scale production of PG for further clinical studies has been considerable.…”

Section: Introductionmentioning

confidence: 99%

Utilization of Crab Waste for Cost-Effective Bioproduction of Prodigiosin

Nguyen

et al. 2020

Marine Drugs

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This study aimed to establish the culture process for the cost-effective production of prodigiosin (PG) from demineralized crab shell powder (de-CSP), a fishery processing byproduct created via fermentation. Among the tested PG-producing strains, Serratia marcescens TNU02 was demonstrated to be the most active strain. Various ratios of protein/de-CSP were used as the sources of C/N for PG biosynthesis. The PG yield was significantly enhanced when the casein/de-CSP ratio was controlled in the range of 3/7 to 4/6. TNU02 produced PG with a high yield (5100 mg/L) in a 15 L bioreactor system containing 4.5 L of a newly-designed liquid medium containing 1.6% C/N source (protein/de-CSP ratio of 3/7), 0.02% (NH4)2SO4, 0.1% K2HPO4, and an initial pH of 6.15, at 27 °C for 8 h in dark conditions. The red pigment was purified from the culture broth and then quantified as being PG by specific Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and UV spectra analysis. The purified PG demonstrated moderate antioxidant and effective inhibition against four cancerous cell lines. Notably, this study was the first to report on using crab wastes for PG bioproduction with high-level productivity (5100 mg/L) in a large scale (4.5 L per pilot) in a short period of fermentation time (8 h). The salt compositions, including (NH4)2SO4 and K2HPO4, were also a novel finding for the enhancement of PG yield by S. marcescens in this report.

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“…A similar kind of intracellular pink-colored bacterial pigment, Prodigiosin was reported from Serratia marcescens using methanol as the extraction solvent. This pigment was also reported with anticancer and antibacterial activity [35,36].…”

Section: Extraction and Purification Of Bacterial Pigmentmentioning

confidence: 79%

Purification and optimization of pink pigment produced by newly isolated bacterial strain Enterobacter sp. PWN1

et al. 2021

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Pigment-producing bacteria were isolated from kitchen wastewaters of the National Institute of Technology, Rourkela. A pink non-virulent bacterial strain PWN1 was selected based on the India Ink Broth and Coomassie Brilliant Blue (R-250) dye assay. According to morphological and biochemical characterization, the strain PWN1was a Gram-negative, rod-shaped, motile, non-coliform bacterium and could utilize only glucose and adonitol as sole carbon source. The pigment was found to be a growth-associated product, and the pigment production was accelerated after 40 h of bacterial culture. Further, 16S rRNA gene-based molecular identification showed its similarity with Enterobacter sp. The pigments were extracted by the solvent extraction method using chloroform and ethanol (3:1). The extracted pigments were then purified through thin-layer chromatography and column chromatography. To maximize pigment production, the culture condition was optimized for maximum biomass production using statistical software Design Expert v13. A quadratic model was structured describing the process efficiently and it suggested a moderate temperature, pH, and a high inoculum concentration which generated biomass of 3.81 ± 0.02 g/L. At optimized condition, 1 L of cell culture produced 3.77 g of biomass which produced a crude pigment of 0.234 g after solvent extraction and 0.131 g after column chromatography, implying a yield of 6.2% for crude pigment and 3.47% for purified pigment from biomass. The yield of the obtained pigment was high enough to draw interest for industrial production, although the application of the pigment is considerable for further study.

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Prodigiosin/PU-H71 as a novel potential combined therapy for triple negative breast cancer (TNBC): preclinical insights

Cited by 38 publications

References 125 publications

Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Targeted Codelivery of Prodigiosin and Simvastatin Using Smart BioMOF: Functionalization by Recombinant Anti-VEGFR1 scFv

Utilization of Crab Waste for Cost-Effective Bioproduction of Prodigiosin

Purification and optimization of pink pigment produced by newly isolated bacterial strain Enterobacter sp. PWN1

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