Activation of human leukemic mast cell line LAD2 is modulated by dehydroleucodine and xanthatin

Vera, Mariano E.; Persia, Fabio Andrés; Mariani, María Laura; Rudolph, M I; Fogal, Teresa; Ceñal, Juan P.; Favier, Laura S.; Tonn, Carlos E.; Penissi, Alicia Beatriz

doi:10.3109/10428194.2012.662644

Cited by 15 publications

(17 citation statements)

References 12 publications

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“…Previous studies showed that xanthatin had an antitumour effect in several tumour cells, including A549 nonsmall cell lung cancer cells, H1299 nonsmall cell lung cancer cells, B16‐F10 murine melanoma cells, human breast cancer MDA‐MB‐231 cells, HL‐60 cells, the human leukemic mast cell line LAD2, and Chinese hamster ovary cells (Li et al, ; Sanchez‐Lamar et al, ; Takeda, Nishimura, et al, ; Takeda, Noguchi, et al, ; Tao et al, ; Tao et al, ; Tao et al, ; Vera et al, ; Yu et al, ; L. Zhang, Ruan, et al, ). Here, we found that xanthatin significantly inhibited tumour growth in both nude mouse xenograft glioma and rat orthotopic implanted glioma in a dose‐dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…Xanthatin, one of the major active compounds of X. strumarium L., has been reported to inhibit the proliferation of tumour cells, such as A549 nonsmall cell lung cancer cells, H1299 non-small cell lung cancer cells, B16-F10 murine melanoma cells, human breast cancer MDA-MB-231 cells, HL-60 cells, the human leukaemic mast cell line LAD2, and Chinese hamster ovary cells (Li et al, 2013;Sanchez-Lamar et al, 2016;Takeda, Noguchi, et al, 2013;Tao et al, 2017;Tao et al, 2013;Tao et al, 2016;Vera et al, 2012;Yu et al, 2015;L. Zhang, Ruan, et al, 2012).…”

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confidence: 99%

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The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging

Wei

et al. 2018

Phytotherapy Research

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To investigate the suppressive effects of xanthatin on glioma growth in a nude mouse xenograft model and rat orthotopic implantation model using magnetic resonance imaging (MRI) to dynamically monitor the antitumour growth and antiangiogenesis effects of xanthatin. The nude mouse xenograft tumour model and rat orthotopic implantation model were established to observe the antitumour effects of xanthatin in vivo. In the rat orthotopic implanted tumour model, MRI scanning was used to dynamically monitor the antitumour growth effect and evaluate the antiangiogenesis effect of xanthatin. We found that xanthatin at a dose of 0.4 mg/10 g dramatically decreased the growth of xenograft tumours in nude mice. The antiangiogenesis effect of xanthatin C6 glioma was evaluated by dynamic contrast-enhanced (DCE) MRI via comparison of the volume transfer constant (K trans ) value, a parameter that reflects vessel permeability. We found that xanthatin at the doses of 8 and 16 mg/kg significantly decreased the K trans value, which suggests that xanthatin has antiangiogenesis effects. These data demonstrate the suppressive effects of xanthatin on C6 glioma occur via antiangiogenesis. Meanwhile, this study also provides evidence for the application of quantitative parameters of DCE-MRI for dynamically evaluating the growth and angiogenesis of intracranial tumours and for experimental and clinical research.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging

Wei

et al. 2018

Phytotherapy Research

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“…It was reported that dehydroleucodine inhibited the degranulation of human leukemic LAD2 mast cells, thus acting as mast cell stabilizers (Vera et al 2012). Interestingly, it was reported that dehydroleucodine-treated cervical cancer HeLa cells became apoptotic, where the greater accumulation of DNA lesions that triggered the activation of ATM were consequently leading to transient G2/M arrest and permanent G1 arrest of HeLa cells (Costantino et al 2013).…”

Section: Artemisia Douglasianamentioning

confidence: 99%

Activation and Inhibition of ATM by Phytochemicals: Awakening and Sleeping the Guardian Angel Naturally

Farooqı

Tang

et al. 2015

Arch. Immunol. Ther. Exp.

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Double-stranded breaks (DSBs) are cytotoxic DNA lesions caused by oxygen radicals, ionizing radiation, and radiomimetic chemicals. Increasing understanding of DNA damage signaling has provided an ever-expanding list of modulators reported to orchestrate DNA damage repair and ataxia telangiectasia mutated (ATM) is the master regulator and main transducer of the DSB response. Increasingly, it is being realized that DNA damage response is a synchronized and branched network that functionalizes different molecular cascades to activate special checkpoints, thus temporarily arresting progression of the cell cycle while damage is being assessed and processed. It is noteworthy that both nutrigenetics and nutrigenomics have revolutionized the field of molecular biology and rapidly accumulating experimental evidence has started to shed light on biological activities of a wide range of phytochemicals reported to modulate cell cycle, DNA repair, cell growth, differentiation and apoptosis as evidenced by cell-based studies. In this review, we have attempted to provide an overview of DNA damage signaling, how ATM signaling regulates tumor necrosis factors-related apoptosis inducing ligand (TRAIL)-induced intracellular network. We also illuminate on how resveratrol, epigallocatechin gallate, curcumin, jaceosidin, cucurbitacin, apigenin, genistein, and others trigger activation of ATM in different cancer cells as well as agents for ATM inactivation. Understanding the interplay of TRAIL-induced intracellular signaling and ATM modulation of downstream effectors is very important. This holds particularly for a reconceptualization of the apparently paradoxical roles and therapeutically targetable for enhancing the response to DNA damage-inducing therapy.

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“…Mast cells are considered divergent in various tissue settings, 1,11 are difficult to obtain at scale for assay purposes from such tissues, and are rare in blood. A few mast cell-like cell lines have been reported in the literature, including HMC-1 cells 12,13 and LAD2 cells, 14,15 although culture of these cell lines remains challenging. We chose to use an approach precedented in the literature, using human primary cord blood-derived mononuclear cells, 7,8,[16][17][18] culturing and differentiating the cells to a mast cell phenotype over many weeks, before screening compounds for antagonism of both tryptase release as a marker of degranulation and PGD 2 synthesis as the major arachidonic acid-derived mediator.…”

Section: +mentioning

confidence: 99%

A Phenotypic Screening Approach in Cord Blood–Derived Mast Cells to Identify Anti-Inflammatory Compounds

et al. 2013

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Mast cells are unique hematopoietic cells that are richly distributed in the skin and mucosal surfaces of the respiratory and gastrointestinal tract. They play a key role in allergic inflammation by releasing a cocktail of granular constituents, including histamine, serine proteases, and various eicosanoids and cytokines. As such, a number of drugs target either inhibition of mast cell degranulation or the products of degranulation. To identify potential novel drugs and mechanisms in mast cell biology, assays were developed to identify inhibitors of mast cell degranulation and activation in a phenotypic screen. Due to the challenges associated with obtaining primary mast cells, cord blood-derived mononuclear cells were reproducibly differentiated to mast cells and assays developed to monitor tryptase release and prostaglandin D 2 generation. The tryptase assay was particularly sensitive, requiring only 500 cells per data point, which permitted a set of approximately 12,000 compounds to be screened robustly and cost-effectively. Active compounds were tested for concomitant inhibition of prostaglandin D2 generation. This study demonstrates the robustness and effectiveness of this approach in the identification of potential novel compounds and mechanisms targeting mast cell-driven inflammation, to enable innovative drug discovery efforts to be prosecuted.

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Activation of human leukemic mast cell line LAD2 is modulated by dehydroleucodine and xanthatin

Cited by 15 publications

References 12 publications

The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging

The antitumour growth and antiangiogenesis effects of xanthatin in murine glioma dynamically evaluated by dynamic contrast‐enhanced magnetic resonance imaging

Activation and Inhibition of ATM by Phytochemicals: Awakening and Sleeping the Guardian Angel Naturally

A Phenotypic Screening Approach in Cord Blood–Derived Mast Cells to Identify Anti-Inflammatory Compounds

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