Investigations regarding the utility of prodigiosenes to treat leukemia

Smithen, Deborah A.; Forrester, A. Michael; Corkery, Dale; Dellaire, Graham; Colpitts, Julie; McFarland, Sherri A.; Berman, Jason N.; Thompson, Alison

doi:10.1039/c2ob26535d

Cited by 23 publications

(29 citation statements)

References 38 publications

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“…The A and B pyrrole rings are directly connected, while the third ring is connected by a methyl bridge [3,4]. These components are synthesized by Gram-positive bacteria and Gram-negative bacteria, such as Pseudomonas, Vibrio, Streptomyces and Serratia, that have antimicrobial activity [5], anti-malarial activity [6,7], immunosuppressive activity [8][9][10], and antitumor activity [11][12][13]. Serratamolide was isolated for the first time in 1961 [14] from a Serratia marcescens.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial Activity of a Novel Depsipeptide and Prodigiosine of Serratia marcescans S823

Zhu¹,

Pang²,

Chen³

et al. 2018

Nat Prod Chem Res

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To investigate the antimicrobial activity of secondary metabolites from Serratia marcescans S823. The strain Serratia marcescans S823 was screened for its antibacterial activity. The active components from the bacterium were isolated by bioactivity-guided analysis. Their structures were identified by chemical and spectroscopic methods to be prodigiosine (PG) (1), serratamolide A (2) and serratamolide G (3), which is a new compound. The MIC and MBC of prodigiosine and serratamolide G were 6.25 μg.mL-1 and 12.5 μg.mL-1 against C. albicans and 6.25 μg.mL-1 and 25 μg.mL-1 against B. thuringiensis respectively. They might be potential alternative treatment options for Candida albicans infection. This study encourages further investigation of natural products as new antibiotics.

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Section: Introductionmentioning

confidence: 99%

Antibacterial Activity of a Novel Depsipeptide and Prodigiosine of Serratia marcescans S823

Zhu¹,

Pang²,

Chen³

et al. 2018

Nat Prod Chem Res

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“…A number of recent zebrafish leukemia xenograft studies indicated that zebrafish are a useful animal model in cancer research and chemotherapeutic drug screening [48]–[50]. Several methods have been developed for the in vitro evaluation of cell proliferation (MTT assay), metastasis (under-agarose migration assay), and angiogenesis (endothelial tube formation assay).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Phenotyping-Based In Vivo Chemical Screening in a Zebrafish Model of Leukemia Stem Cell Xenotransplantation

et al. 2014

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Zebrafish-based chemical screening has recently emerged as a rapid and efficient method to identify important compounds that modulate specific biological processes and to test the therapeutic efficacy in disease models, including cancer. In leukemia, the ablation of leukemia stem cells (LSCs) is necessary to permanently eradicate the leukemia cell population. However, because of the very small number of LSCs in leukemia cell populations, their use in xenotransplantation studies (in vivo) and the difficulties in functionally and pathophysiologically replicating clinical conditions in cell culture experiments (in vitro), the progress of drug discovery for LSC inhibitors has been painfully slow. In this study, we developed a novel phenotype-based in vivo screening method using LSCs xenotransplanted into zebrafish. Aldehyde dehydrogenase-positive (ALDH+) cells were purified from chronic myelogenous leukemia K562 cells tagged with a fluorescent protein (Kusabira-orange) and then implanted in young zebrafish at 48 hours post-fertilization. Twenty-four hours after transplantation, the animals were treated with one of eight different therapeutic agents (imatinib, dasatinib, parthenolide, TDZD-8, arsenic trioxide, niclosamide, salinomycin, and thioridazine). Cancer cell proliferation, and cell migration were determined by high-content imaging. Of the eight compounds that were tested, all except imatinib and dasatinib selectively inhibited ALDH+ cell proliferation in zebrafish. In addition, these anti-LSC agents suppressed tumor cell migration in LSC-xenotransplants. Our approach offers a simple, rapid, and reliable in vivo screening system that facilitates the phenotype-driven discovery of drugs effective in suppressing LSCs.

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“…K562 (an erythroleukemia from BCR-ABL1 + CML) and Jurkat (a PTEN -null, NOTCH1 -mutant T-ALL) were transplanted into embryos, and imatinib and cyclophosphamide responses were seen [89]. Similar findings were reported in a second study with imatinib and K562, and with all- trans -retinoic acid in NB4 (a PML-RARA + APML) [88], and then expanded further by testing investigational molecules against K562 in the same system [93]. If xeno-transplant can move beyond cell lines to include patient samples, “personalized medicine” assays could truly become viable.…”

Section: Research Applications Of Zebrafish Leukemia Modelsmentioning

confidence: 96%

“…Some of these molecules are in the pipeline for eventual clinical use, while others are reagents to inhibit key pathways, acting as surrogates for drugs with similar activity not yet developed. Human leukemic xeno-transplants have also been tested in fish [88, 89, 93]. Here, the biologic question is different: rather than testing agents for activity against the same type of leukemia from disparate species, the query is whether fish-based systems can provide templates for pre-clinical assays.…”

Section: Research Applications Of Zebrafish Leukemia Modelsmentioning

confidence: 99%

Danio rerio: Small Fish Making a Big Splash in Leukemia

Squiban

Frazer

2014

Curr Pathobiol Rep

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Zebrafish (Danio rerio) are widely used for developmental biology studies. In the past decade, D. rerio have become an important oncology model as well. Leukemia is one type of cancer where zebrafish are particularly valuable. As vertebrates, fish have great anatomic and biologic similarity to humans, including their hematopoietic and immune systems. As an experimental platform, D. rerio offer many advantages that mammalian models lack. These include their ease of genetic manipulation, capacity for imaging, and suitability for large-scale phenotypic and drug screens. In this review, we present examples of these strategies and others to illustrate how zebrafish have been and can be used to study leukemia. Besides appraising the techniques researchers apply and introducing the leukemia models they have created, we also highlight recent and exciting discoveries made using D. rerio with an eye to where the field is likely headed.

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Investigations regarding the utility of prodigiosenes to treat leukemia

Cited by 23 publications

References 38 publications

Antibacterial Activity of a Novel Depsipeptide and Prodigiosine of Serratia marcescans S823

Antibacterial Activity of a Novel Depsipeptide and Prodigiosine of Serratia marcescans S823

Quantitative Phenotyping-Based In Vivo Chemical Screening in a Zebrafish Model of Leukemia Stem Cell Xenotransplantation

Danio rerio: Small Fish Making a Big Splash in Leukemia

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