The Use of Glaucarubin (a Crystalline Glycoside Isolated from Simarouba Glauca) in the Treatment of Human Colonic Amebiasis

Assendelft, Frederik Van; Miller, Jay W.; Mintz, D T; Schack, Jerome A.; Ottolenghi, P; Most, Harry

doi:10.4269/ajtmh.1956.5.501

Cited by 11 publications

(7 citation statements)

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“…It originates from the paradise tree, or Simarouba glauca . Glaucarubine is known to act against amebiasis [39]. A closely related compound, glaucarubinone, has been shown to have a variety of anticancer activities, originating from its inhibition of protein synthesis [40].…”

Section: Resultsmentioning

confidence: 99%

Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured by Imaging Flow Cytometry

Heisler

Elvir

Barnouti

et al. 2014

Nat. Prod. Bioprospect.

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Gaining a full understanding of the mechanisms of action of natural products as therapeutic agents includes observing the effects of natural products on cellular morphology, because abnormal cellular morphology is an important aspect of cellular transformations that occur as part of disease states. In this study a set of natural products was examined in search of small molecules that influence the cylindrical morphology of fission yeast Schizosaccharomyces pombe. Imaging flow cytometry of large populations of S. pombe exposed to natural products captured cell images and revealed changes in mean length and aspect ratio of cells. Several natural products were found to alter S. pombe’s morphology relative to control, in terms of elongating cells, shrinking them, or making them more round. These results may facilitate future investigations into methods by which cells establish and maintain specific shapes.Graphical AbstractGaining a full understanding of the mechanisms of action of natural products as therapeutic agents includes observing the effects of natural products on cellular morphology, because abnormal cellular morphology is an important aspect of cellular transformations that occur as part of disease states. In this study a set of natural products was examined in search of small molecules that influence the cylindrical morphology of fission yeast Schizosaccharomyces pombe. Imaging flow cytometry of large populations of S. pombe exposed to natural products captured cell images and revealed changes in mean length and aspect ratio of cells. Several natural products were found to alter S. pombe’s morphology relative to control, in terms of elongating cells, shrinking them, or making them more round. These results may facilitate future investigations into methods by which cells establish and maintain specific shapes.

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Section: Resultsmentioning

confidence: 99%

Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured by Imaging Flow Cytometry

Heisler

Elvir

Barnouti

et al. 2014

Nat. Prod. Bioprospect.

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“…In this study, we performed a compound screening and identified the natural product glaucarubin as a potent inhibitor that can specifically repress the growth of MCPyV-positive MCC cells. Glaucarubin is a crystalline glycoside extracted from the tropical plant Simarouba glauca [48]. We discovered that glaucarubin could specifically inhibit the growth of MCPyV-positive cells such as MKL-1 at low concentrations (with an IC50 of nearly 149 nM), without introducing much toxicity for control MCPyV-negative MCC and healthy skin cells, even at very high concentrations (IC50 ranges from 4.48 to 157 µM).…”

Section: Discussionmentioning

confidence: 99%

“…Glaucarubin has been used as an herbal medicine for treating intestinal amoebiasis for more than six decades [48,60,61]. In addition, ABT-199 is an FDA-approved anticancer drug.…”

Section: Discussionmentioning

confidence: 99%

Combining DNA Damage Induction with BCL-2 Inhibition to Enhance Merkel Cell Carcinoma Cytotoxicity

Liu

Krump

Herlyn

et al. 2020

Biology

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Merkel cell carcinoma (MCC) is a highly lethal skin cancer. MCC tumors rapidly develop resistance to the chemotherapies tested to date. While PD-1/PD-L1 immune checkpoint blockade has demonstrated success in MCC treatment, a significant portion of MCC patients are nonresponsive. Therefore, the pressing need for effective MCC chemotherapies remains. We screened a library of natural products and discovered that one compound, glaucarubin, potently reduced the viability of Merkel cell polyomavirus (MCPyV)-positive MCCs, while remaining nontoxic to primary human fibroblasts and MCPyV-negative MCC cell lines tested. Protein array and Western blot analyses revealed that glaucarubin induces DNA damage and PARP-1 cleavage that correlates with the loss of viability in MCC cells. However, high basal expression of the antiapoptotic factor BCL-2 allowed a subpopulation of cells to survive glaucarubin treatment. Previous studies have shown that, while targeting BCL-2 family proteins significantly decreases MCC cell viability, BCL-2 antisense therapy alone was insufficient to inhibit tumor growth in patients with advanced MCC. We discovered that treatment with an FDA-approved BCL-2 inhibitor in the context of glaucarubin-induced DNA damage led to near complete killing in multiple MCPyV-positive MCC cell lines that express high levels of BCL-2. The combination of DNA damage-induced apoptosis and BCL-2 inhibition thus represents a novel therapeutic strategy for MCPyV-positive MCCs.

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“…Ipecacuanha, is an antiamoebic Brazilian root, first taken to Europe by Piso in 1658, and it was not until the mid nineteenth century that its principle alkaloid, emetine, was tested on dysenteric stools against E. histolytica and in the cure of amoebic dysentery. Glaucarubin, a quassinoid isolated from Simarouba glauca, was found to have in vitro amoebicidal activity and its chemistry and relative toxicity were reported in the late 1940's (Van Assendelft et al, 1956).…”

Section: Introductionmentioning

confidence: 99%

A review of plant species assessedin?vitro for antiamoebic activity or both antiamoebic and antiplasmodial properties

Sharma

2001

Phytother. Res.

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The Use of Glaucarubin (a Crystalline Glycoside Isolated from Simarouba Glauca) in the Treatment of Human Colonic Amebiasis

Cited by 11 publications

References 0 publications

Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured by Imaging Flow Cytometry

Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured by Imaging Flow Cytometry

Combining DNA Damage Induction with BCL-2 Inhibition to Enhance Merkel Cell Carcinoma Cytotoxicity

A review of plant species assessedin?vitro for antiamoebic activity or both antiamoebic and antiplasmodial properties

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