Phytochemical Inhibition of Multidrug Resistance Protein-1 as a Therapeutic Strategy for Hemangioendothelioma

Biswas, Ayan; Clark, Emma Chichester; Sen, Chandan K.

doi:10.1089/ars.2016.6881

Cited by 4 publications

(19 citation statements)

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“…The NBE dose (200 lg/mL) and pretreatment duration were deter-mined using previously reported toxicity and dose/response studies for EOMA cells (4). Nontumor forming murine aortic endothelial (MAE) cells were used as controls (11,12). Time and dose responses to XRT were analyzed using LDH and propidium iodide (PI) exclusion assays to identify the threshold dose of XRT needed to induce cell toxicity (Fig.…”

Section: Sensitization Of Tumor Forming Endothelial Cells To Effects Of Xrt Is Time and Dose Dependentmentioning

confidence: 99%

“…Kaposiform HE features several solid poorly circumscribed nodules such that each nodule is composed of a mixture of small capillaries and solid lobules of endothelial cells arranged in a glomeruloid pattern. Mouse hemangioendothelioma endothelial (EOMA) cells are a validated experimental model to study mechanisms in HE and its management (11,12,23).…”

Section: Introductionmentioning

confidence: 99%

“…On the contrary, specific phytochemicals such as anthocyanins are known to act on a number of specific molecular mechanisms that inhibit tumorigenesis (56). Our recent work has identified that a standardized anthocyanin-rich natural berry extract (NBE) is effective in prolonging survival of HE bearing mice (11). The objective of this work is to investigate tumor mitochondrial function and its significance in the development of HE, as well as in the survival of HE-bearing mice.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondria as Target for Tumor Management of Hemangioendothelioma

Biswas

Singh

Sen

et al. 2021

Antioxidants & Redox Signaling

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Aims: Hemangioendothelioma (HE) may be benign or malignant. Mouse hemangioendothelioma endothelial (EOMA) cells are validated to study mechanisms in HE. This work demonstrates that EOMA cells heavily rely on mitochondria to thrive. Thus, a combination therapy, including weak X-ray therapy (XRT, 0.5 Gy) and a standardized natural berry extract (NBE) was tested. This NBE is known to be effective in managing experimental HE and has been awarded with the Food and Drug Administration Investigational New Drug (FDA-IND) number 140318 for clinical studies on infantile hemangioma. Results: NBE treatment alone selectively attenuated basal oxygen consumption rate of EOMA cells. NBE specifically sensitized EOMA, but not murine aortic endothelial cells to XRT-dependent attenuation of mitochondrial respiration and adenosine triphosphate (ATP) production. Combination treatment, selectively and potently, influenced mitochondrial dynamics in EOMA cells such that fission was augmented. This was achieved by lowering of mitochondrial sirtuin 3 (SIRT3) causing increased phosphorylation of AMP-activated protein kinase (AMPK). A key role of SIRT3 in loss of EOMA cell viability caused by the combination therapy was evident when pyrroloquinoline quinone, an inducer of SIRT3, pretreatment rescued these cells. Innovation and Conclusion: Mitochondria-targeting NBE significantly extended survival of HE-affected mice. The beneficial effect of NBE in combination with weak X-ray therapy was, however, far more potent with threefold increase in murine survival. The observation that safe natural products may target tumor cell mitochondria and sharply lower radiation dosage required for tumor management warrants clinical testing. Antioxid. Redox Signal. 34,[137][138][139][140][141][142][143][144][145][146][147][148][149][150][151][152][153]

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Section: Sensitization Of Tumor Forming Endothelial Cells To Effects Of Xrt Is Time and Dose Dependentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitochondria as Target for Tumor Management of Hemangioendothelioma

Biswas

Singh

Sen

et al. 2021

Antioxidants & Redox Signaling

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“…A study by Biswas and co-workers [80], evaluated the inhibitory activities of phytochemical compounds on multidrug resistance in cancer and proposed the mechanisms by which standardized berry extracts inhibit the endothelial cell tumour growth for hemangiomas. The study further established that natural berry extracts considerably inhibited the actions of multidrug resistance protein-1 (MRP-1) in EOMA cells when compared with controls.…”

Section: An Overview Of Phytochemical Interactions and Stimulations Omentioning

confidence: 99%

“…The study further established that natural berry extracts considerably inhibited the actions of multidrug resistance protein-1 (MRP-1) in EOMA cells when compared with controls. The inhibition of MRP-1 resulted in apoptotic tumour cell death via the accumulation of oxidized glutathione (GSSG) in the nucleus of EOMA cells where there is hyperactiveness of NADPH oxidase thereby causing angiogenesis pathology [80].…”

Section: An Overview Of Phytochemical Interactions and Stimulations Omentioning

confidence: 99%

Phytodentistry in Africa: prospects for head and neck cancers

et al. 2021

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Background Orthodox dentistry has undergone significant changes in recent times with the introduction of various omics and molecular targeted therapies both at the experimental/trial and clinical implementation level. Although, significant milestones have been achieved in the molecular dentistry field in the past decade, there remains a dearth of application of phytopharmacological innovation in personalized and targeted therapies for dental diseases. Main body From time immemorial, plant products have long been an integral aspect of dental practice ranging from chewing sticks/herbal kinds of toothpaste to dental/impression materials. The current era of precision medicine seeks to apply a multipronged molecular and bio-computational approaches to solve fundamental medical problems that have hitherto remained difficult. Remarkable changes in the molecular/omics era, have transformed empirical therapies into personalized/individualized ones. Furthermore, the combinatorial application and the widespread introduction of high-throughput molecular tools such as pharmacogenomics, phytopharmacology, metabolomics, mathematical modelling, and genetic engineering inter alia, has tremendously improved the diagnostic and therapeutic landscape of medicine. Additionally, the variable molecular epidemiology of diseases among different population and emerging molecular evidence warrants the use of customized novel theranostic techniques. Unfortunately, the footprint of such emerging application is sparse in dental diseases such as maxillofacial cancers. Conclusion Hence, this review seeks to evaluate the potential application of phytopharmacological approaches to head and neck cancers in a resource-limited environment, such as Africa.

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Fucoidan suppresses proliferation and epithelial‐mesenchymal transition process via Wnt/β‐catenin signalling in hemangioma

Zhu,

Luo,

et al. 2024

Experimental Dermatology

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Hemangioma is a common benign tumour that usually occurs on the skin of the head and neck, particularly among infants. The current clinical treatment against hemangioma is surgery excision, however, application of drug is a safer and more economical therapy for children suffering from hemangioma. As a natural sulfated polysaccharide rich in brown algae, fucoidan is widely recognized for anti‐tumour bioactivity and dosage safety in humans. This study aims to demonstrate the anti‐tumour effect and underlying mechanism of fucoidan against hemangioma in vivo and in vitro. We investigated the effects of fucoidan by culturing hemangioma cells in vitro and treating BALB/c mice bearing with hemangioma. At first, we measured the cell proliferation and migration ability through in vitro experiments. Then, we tested the expression of epithelial‐mesenchymal transition (EMT) and Wnt/β‐catenin pathway‐related biomarkers by western blot and qPCR. Furthermore, we applied β‐catenin‐specific inhibitor, XAV939, to determine whether fucoidan suppressed EMT via the Wnt/β‐catenin pathway in hemangioma cells. In vivo experiments, we applied oral gavage of fucoidan to treat EOMA‐bearing mice, along with evaluating the safety and efficacy of fucoidan. We found that fucoidan remarkably inhibits the proliferation and EMT ability of hemangioma cells, which is dependent on the Wnt/β‐catenin pathway. These results suggest that fucoidan exhibits tumour inhibitory effect on aggressive hemangioma via regulating the Wnt/β‐catenin signalling pathway both in vitro and in vivo, providing a new potent drug candidate for treating hemangioma.

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Phytochemical Inhibition of Multidrug Resistance Protein-1 as a Therapeutic Strategy for Hemangioendothelioma

Abstract: These findings indicate that berry extract inhibition of MRP-1 merits consideration and further investigation as a therapeutic intervention and may have application for other cancers with elevated MRP-1 activity. Antioxid. Redox Signal. 26, 1009-1019.

Cited by 4 publications

References 54 publications

Mitochondria as Target for Tumor Management of Hemangioendothelioma

Mitochondria as Target for Tumor Management of Hemangioendothelioma

Phytodentistry in Africa: prospects for head and neck cancers

Fucoidan suppresses proliferation and epithelial‐mesenchymal transition process via Wnt/β‐catenin signalling in hemangioma

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