Antileukemic Effect of Epirubicin Conjugated with Chitosan Against Mouse P388 Ascitic Leukemia

Todorova, N.; Maneva, K.; Ilarionova, M.; Dudov, A.; Todorov, D.

doi:10.1080/13102818.2003.10817074

Cited by 7 publications

(6 citation statements)

References 8 publications

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“…Chronic upregulation of Wnt signaling has been observed in several cancers and was also reported to play an important role in CSC [46]. Therefore, this observation is generally consistent with the decrease in tumorigenicity and aggressiveness of P388 cancer cells upon SP1049C treatments, as well as with the increase in tumorigenicity and aggressiveness of cancer cells upon Dox alone treatment [34], [50]. However, the functional significance of the observed changes in Wnt/β-catenin signaling pathway has not been demonstrated in this study and remains to be further explored.…”

Section: Discussionsupporting

confidence: 85%

“…This protocol ensured that in each given passage the animals did not become moribund due to growing ascitic cells. For example, it was reported that without treatment the BDF1 mouse with P388 ascitic cells has a mean survival time of approximately 10.3 days [34]. Our prior study has shown that using similar protocol the drug treatments extended the survival and well-being of animals with the P388 ascitic cells [25].…”

Section: Resultsmentioning

confidence: 88%

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Effect of Doxorubicin/Pluronic SP1049C on Tumorigenicity, Aggressiveness, DNA Methylation and Stem Cell Markers in Murine Leukemia

Alakhova

Zhao

et al. 2013

PLoS ONE

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PurposePluronic block copolymers are potent sensitizers of multidrug resistant cancers. SP1049C, a Pluronic-based micellar formulation of doxorubicin (Dox) has completed Phase II clinical trial and demonstrated safety and efficacy in patients with advanced adenocarcinoma of the esophagus and gastroesophageal junction. This study elucidates the ability of SP1049C to deplete cancer stem cells (CSC) and decrease tumorigenicity of cancer cells in vivo.Experimental DesignP388 murine leukemia ascitic tumor was grown in BDF1 mice. The animals were treated with: (a) saline, (b) Pluronics alone, (c) Dox or (d) SP1049C. The ascitic cancer cells were isolated at different passages and examined for 1) in vitro colony formation potential, 2) in vivo tumorigenicity and aggressiveness, 3) development of drug resistance and Wnt signaling activation 4) global DNA methylation profiles, and 5) expression of CSC markers.ResultsSP1049C treatment reduced tumor aggressiveness, in vivo tumor formation frequency and in vitro clonogenic potential of the ascitic cells compared to drug, saline and polymer controls. SP1049C also prevented overexpression of BCRP and activation of Wnt-β-catenin signaling observed with Dox alone. Moreover, SP1049C significantly altered the DNA methylation profiles of the cells. Finally, SP1049C decreased CD133+ P388 cells populations, which displayed CSC-like properties and were more tumorigenic compared to CD133− cells.ConclusionsSP1049C therapy effectively suppresses the tumorigenicity and aggressiveness of P388 cells in a mouse model. This may be due to enhanced activity of SP1049C against CSC and/or altered epigenetic regulation restricting appearance of malignant cancer cell phenotype.

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Section: Discussionsupporting

confidence: 85%

Section: Resultsmentioning

confidence: 88%

Effect of Doxorubicin/Pluronic SP1049C on Tumorigenicity, Aggressiveness, DNA Methylation and Stem Cell Markers in Murine Leukemia

Alakhova

Zhao

et al. 2013

PLoS ONE

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“…administration of 12.5-40 mg/m 2 DOXO equivalent conjugate every 21-28 days to 13 patients [48] showed that the maximum tolerated dose is 40 mg/m 2 . However, Dex-DOXO failed the Phase I probably because of the toxicity of the oxidized Dex carrier.…”

Section: Doxorubicinmentioning

confidence: 98%

“…In conclusion, the conjugate presents several advantages over the free epirubicin: lower toxicity, stronger antileukemic activity, and higher therapeutic index [48]. …”

Section: Epirubicinmentioning

confidence: 99%

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Polysaccharide-Based Anticancer Prodrugs

Caliceti

Salmaso

Bersani

2009

Macromolecular Anticancer Therapeutics

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So far, polysaccharides have been widely used in pharmaceutical technology as first choice excipients for production of traditional formulations. Nevertheless, in the recent years these natural and semisynthetic macromolecules have been addressed for new challenging applications as functional materials for innovative formulations. Their peculiar physicochemical and biological properties have been exploited to develop macromolecular prodrugs which can exhibit favorable biopharmaceutical properties and enforce the therapeutic performance of the parent drugs. These polymers display, in fact, high biocompatibility and biodegradability, multiple insertion points, and biological properties that can be advantageously exploited in drug delivery. In particular, the multifunctional structures of these polymers are anchoring points for conjugation of several anticancer drugs, which usually suffer from poor physicochemical, biopharmaceutical, and therapeutic properties that limit their therapeutic performance and proper use in anticancer treatment. Polysaccharide-based anticancer prodrugs can be designed to endow derivatives with new bioresponse, targeting, or environmental triggering properties or to combine molecules with synergistic therapeutic effect. Over the years, a variety of synthetic protocols have been set up to conjugate anticancer drugs to the polysaccharide backbone via specific linkages or through spacers which convey to the conjugates selective drug-delivery properties. Furthermore, the intrinsic antitumor activity and cell-targeting properties of few polysaccharides represent an additional value to the final therapeutic systems. Anticancer drugs with different pharmacodynamic, pharmacokinetic, and physicochemical properties have been successfully conjugated to various natural and semisynthetic polysaccharides highlighting the interesting perspectives for exploitation of new promising anticancer polymer therapeutics.

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PEGylated dendritic nanoarchitechture improves mean survival time of BDF1 mice bearing myelogenous k -562 leukemia

Karthikeyan

Kumar

2013

Journal of Acute Disease

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Antileukemic Effect of Epirubicin Conjugated with Chitosan Against Mouse P388 Ascitic Leukemia

Cited by 7 publications

References 8 publications

Effect of Doxorubicin/Pluronic SP1049C on Tumorigenicity, Aggressiveness, DNA Methylation and Stem Cell Markers in Murine Leukemia

Effect of Doxorubicin/Pluronic SP1049C on Tumorigenicity, Aggressiveness, DNA Methylation and Stem Cell Markers in Murine Leukemia

Polysaccharide-Based Anticancer Prodrugs

PEGylated dendritic nanoarchitechture improves mean survival time of BDF1 mice bearing myelogenous k -562 leukemia

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