Anti-Proliferative Effects of Novel Glyco-Lipid-Arsenicals (III) on MCF-7 Human Breast Cancer Cells

Wimmer, Norbert; Robinson, J. A.; Gopisetty-Venkata, Nagaraj; Roberts‐Thomson, Sarah J.; Monteith, Gregory R.; Tóth, István

doi:10.2174/157340606775197714

Cited by 13 publications

(9 citation statements)

References 28 publications

(50 reference statements)

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“…27 Some glycol-lipid-arsenicals were synthesized based on p-aminophenylarsine oxide (PAPAO) by attaching a lipoamino acid to a sugar, and they were shown to have differential antiproliferative effects on MCF-7 human breast cancer cells. 28 The conjugation with lipoamino acids could protect the trivalent arsenical from oxidation and polymerization and enhance membrane permeability by increasing its lipophilicity. However, the arsenolipids by themselves were judged to be inadequate for therapeutic applications.…”

Section: Chris Lementioning

confidence: 99%

Therapeutic and analytical applications of arsenic binding to proteins

et al. 2015

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Arsenic binding to proteins plays a pivotal role in the health effects of arsenic. Further knowledge of arsenic binding to proteins will advance the development of bioanalytical techniques and therapeutic drugs. This review summarizes recent work on arsenic-based drugs, imaging of cellular events, capture and purification of arsenic-binding proteins, and biosensing of arsenic. Binding of arsenic to the promyelocytic leukemia fusion oncoprotein (PML-RARα) is a plausible mode of action leading to the successful treatment of acute promyelocytic leukemia (APL). Identification of other oncoproteins critical to other cancers and the development of various arsenicals and targeted delivery systems are promising approaches to the treatment of other types of cancers. Techniques for capture, purification, and identification of arsenic-binding proteins make use of specific binding between trivalent arsenicals and the thiols in proteins. Biarsenical probes, such as FlAsH-EDT2 and ReAsH-EDT2, coupled with tetracysteine tags that are genetically incorporated into the target proteins, are used for site-specific fluorescence labelling and imaging of the target proteins in living cells. These allow protein dynamics and protein-protein interactions to be studied. Arsenic affinity chromatography is useful for purification of thiol-containing proteins, and its combination with mass spectrometry provides a targeted proteomic approach for studying the interactions between arsenicals and proteins in cells. Arsenic biosensors evolved from the knowledge of arsenic resistance and arsenic binding to proteins in bacteria, and have now been developed into analytical techniques that are suitable for the detection of arsenic in the field. Examples in the four areas, arsenic-based drugs, imaging of cellular events, purification of specific proteins, and arsenic biosensors, demonstrate important therapeutic and analytical applications of arsenic protein binding.

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Section: Chris Lementioning

confidence: 99%

Therapeutic and analytical applications of arsenic binding to proteins

et al. 2015

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“…Human osteopontin is composed of 314 amino acid residues containing two crucial functional domains, the calcium-binding domain and arginine-glycine-aspartic acid (RGD) sequences [11]. It is a multifunctional cytokine which mediates in bone resorption, atherosclerosis, angiogenesis, wound repair, immune function, tissue injuries, and disease formation [12,13]. Osteopontin expression has been associated with cancer markers for many years [14].…”

Section: Introductionmentioning

confidence: 99%

FLJ10540 is associated with tumor progression in nasopharyngeal carcinomas and contributes to nasopharyngeal cell proliferation, and metastasis via osteopontin/CD44 pathway

Chen

Shiu

et al. 2012

J Transl Med

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BackgroundNasopharyngeal carcinoma (NPC) is well-known for its highly metastatic characteristics, but little is known of its molecular mechanisms. New biomarkers that predict clinical outcome, in particular the ability of the primary tumor to develop metastatic tumors are urgently needed. The aim of this study is to investigate the role of FLJ10540 in human NPC development.MethodsA bioinformatics approach was used to explore the potentially important regulatory genes involved in the growth/metastasis control of NPC. FLJ10540 was chosen for this study. Two co-expression strategies from NPC microarray were employed to identify the relationship between FLJ10540 and osteopontin. Quantitative-RT-PCR, immunoblotting, and immunohistochemistry analysis were used to investigate the mRNA and protein expression profiles of FLJ10540 and osteopontin in the normal and NPC tissues to confirm microarray results. TW01 and Hone1 NPC cells with overexpression FLJ10540 or siRNA to repress endogenous FLJ10540 were generated by stable transfection to further elucidate the molecular mechanisms of FLJ10540-elicited cell growth and metastasis under osteopontin stimulation.ResultsWe found that osteopontin expression exhibited a positive correlation with FLJ10540 in NPC microarray. We also demonstrated comprehensively that FLJ10540 and osteopontin were not only overexpressed in NPC specimens, but also significantly correlated with advanced tumor and lymph node-metastasis stages, and had a poor 5-year survival rate, respectively. Stimulation of NPC parental cells with osteopontin results in an increase in FLJ10540 mRNA and protein expressions. Functionally, FLJ10540 transfectant alone, or stimulated with osteopontin, exhibited fast growth and increased metastasis as compared to vehicle control with or without osteopontin stimulation. Conversely, knockdown of FLJ10540 by siRNA results in the suppression of NPC cell growth and motility. Treatment with anti-CD44 antibodies in NPC parental cells not only resulted in a decrease of FLJ10540 protein, but also affected the abilities of FLJ10540-elicited cell growth and motility in osteopontin stimulated-NPC cells.ConclusionsThese findings suggest that FLJ10540 may be critical regulator of disease progression in NPC, and the underlying mechanism may involve in the osteopontin/CD44 pathway.

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“…[2] Also synthetic arsenic-glyco derivatives are not new in the literature. Wimmer et al [3] proposed an arsenical glycolipid in which a glucose moiety was conjugated with the aim of improving chemical-physical properties of the drug (Figure 1). Aiming at the design of an arsenic-based anticancer drug, we envision to exploit the preferential uptake of glucose by cancer cells, known as Warburg effect.…”

Section: Introductionmentioning

confidence: 99%

Arsenical C‐Glucoside Derivatives with Promising Antitumor Activity

D’Orazio

Parisi²,

Policano³

et al. 2015

Eur J Org Chem

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C‐Glucoside derivatives covalently linked to the arsenic atom in different oxidation states have been synthesized by avoiding protection‐deprotection steps. While compound 1, bearing an AsV atom, did not show any significant biological activity, compound 2, in which the glucose moiety is linked to the arsenic atom as dithioarsenical (AsIII), showed promising antiproliferative activity on a cell line of neuroblastoma (SK‐N‐BE).

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Anti-Proliferative Effects of Novel Glyco-Lipid-Arsenicals (III) on MCF-7 Human Breast Cancer Cells

Cited by 13 publications

References 28 publications

Therapeutic and analytical applications of arsenic binding to proteins

Therapeutic and analytical applications of arsenic binding to proteins

FLJ10540 is associated with tumor progression in nasopharyngeal carcinomas and contributes to nasopharyngeal cell proliferation, and metastasis via osteopontin/CD44 pathway

Arsenical C‐Glucoside Derivatives with Promising Antitumor Activity

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