The Effect of Cantharidin on Epithelial Cells in Tissue Culture**From the Department of Dermatology, College of Physicians &amp; Surgeons, Columbia University, 10032, and the Department of Obstetrics and Gynecology, College of Physicians &amp; Surgeons, Columbia University.

Einbinder, Julia M.; Parshley, Mary S.; Walzer, Richard; Sanders, Saul L.

doi:10.1038/jid.1969.46

Cited by 10 publications

(1 citation statement)

References 13 publications

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“…[4] Since this initial reference, use of the natural product 1 in western medicine has been limited, conceivably due to its toxicity, and in particular nephrotoxicity. [5][6][7][8][9][10][11][12][13][14][15] More recently, cantharidin (1) has been shown to inhibit cell growth in various tumour cell lines including cervical, tongue, ginival, mucoepidermoid, adenocystic, neuronal, bone, leukaemia, ovarian, and colon cancer,with GI 50 values of 1.3-15 mm. [1-3, 9-11, 16-20] Cantharidin (1) and its analogues, such as norcantharidin (2), are known inhibitors of serine/threonine protein phosphatase.…”

Section: Introductionmentioning

confidence: 99%

Norcantharidin Analogues: Synthesis, Anticancer Activity and Protein Phosphatase 1 and 2A Inhibition

et al. 2008

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Cantharidin (1) and its derivatives are of significant interest as serine/threonine protein phosphatase 1 and 2A inhibitors. Additionally, compounds of this type have displayed growth inhibition of various tumour cell lines. To further explore both of these inhibition pathways, a number of amide-acid norcantharidin analogues (15-26) were prepared. Compounds 23 and 24, containing two carboxylic acid residues, showed good PP1 and PP2A activity, with IC(50) values of approximately 15 and approximately 3 mum, respectively. Substituted aromatic amide analogues 45, 48, 49, 52, 53, and 54 also displayed good PP1 and PP2A inhibition, with IC(50) values in the range of 15-10 microM (PP1) and 11-5 microM (PP2A). However, bulky ortho substituents on the aromatic ring caused the aromatic ring to be skewed from the NCO planarity, leading to a decrease in PP1 and PP2A inhibition. A number of analogues, 20, 22, 25 and 46, showed excellent tumour growth inhibition, with 46 in particular being more potent than the lead, norcantharidin 2.

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Section: Introductionmentioning

confidence: 99%

Norcantharidin Analogues: Synthesis, Anticancer Activity and Protein Phosphatase 1 and 2A Inhibition

et al. 2008

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The effect of cantharidins on leukemic stem cells

Dorn

Kou

Png

et al. 2009

Intl Journal of Cancer

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To identify an agent with specific activity against leukemic stem cells (LSCs), we evaluated compounds that targeted hepatic leukemia factor (HLF), a gene implicated in hematopoietic stem cell (HSCs) regulation, that we found overexpressed in LSCs. Cantharidin, a natural toxin from blister beetles, used as medicinal agent since antiquity, has been described to modulate the HLF competitor NFIL3 and is under clinical evaluation as an antitumor and antimetastatic agent. The molecule is not a substrate for multidrug resistant pumps and does not cause myelosuppression, and therefore it represents a promising compound for selective ablation of LSCs. Cantharidin and norcantharidin, a derivative with reduced toxicity, decreased HLF protein levels and induced apoptosis in the AML cell line MV4‐11 by modulating the expression of several molecules that govern survival pathway, including HLF, SLUG, NFIL3 and c‐myc, thereby inducing p53 and the mitochondrial caspase cascade. In vitro, cantharidin readily targeted primary AML stem and progenitor cells in contrast to conventional chemotherapeutic agents, such as Ara‐C and daunorubicin, that mainly targeted more differentiated leukemic cells. In vitro the compound did not exhibit a therapeutic window, being equally toxic to normal HSCs and LSCs. In vivo cantharidin did not produce myelosuppression. Because of dose‐limiting toxicity in vivo, neither cantharidin nor norcantharidin proved therapeutical benefit in AML xenograft models as a single agent. However, its potent in vitro LSC activity and pathway targeting may still be exploited clinically with a new generation of cantharidin derivatives or formulations and with appropriate drug combinations. © 2008 Wiley‐Liss, Inc.

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Arbeitsphysiologie der Hornschicht in Grundzügen

Klaschka

1979

Normale Und Pathologische Physiologie Der Haut II

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The Effect of Cantharidin on Epithelial Cells in Tissue Culture**From the Department of Dermatology, College of Physicians & Surgeons, Columbia University, 10032, and the Department of Obstetrics and Gynecology, College of Physicians & Surgeons, Columbia University.

Cited by 10 publications

References 13 publications

Norcantharidin Analogues: Synthesis, Anticancer Activity and Protein Phosphatase 1 and 2A Inhibition

Norcantharidin Analogues: Synthesis, Anticancer Activity and Protein Phosphatase 1 and 2A Inhibition

The effect of cantharidins on leukemic stem cells

Arbeitsphysiologie der Hornschicht in Grundzügen

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