1-Methoxy-canthin-6-one induces c-Jun NH2-terminal kinase-dependent apoptosis and synergizes with tumor necrosis factor-related apoptosis-inducing ligand activity in human neoplastic cells of hematopoietic or endodermal origin

Cancer Research
Massimo AmmiranteVincenzo De Feo

Abstract

We investigated the effects of 1-methoxy-canthin-6-one, isolated from the medicinal plant Ailanthus altissima Swingle, on apoptosis in human leukemia (Jurkat), thyroid carcinoma (ARO and NPA), and hepatocellular carcinoma (HuH7) cell lines. Cultures incubated with the compound showed >50% of sub-G1 (hypodiploid) elements in flow cytometry analysis; the apoptosis-inducing activity was evident at <10 micromol/L and half-maximal at about 40 micromol/L 1-methoxy-canthin-6-one. The appearance of hypodiploid elements was preceded by mitochondrial membrane depolarization, mitochondrial release of cytochrome c, and Smac/DIABLO and procaspase-3 cleavage. We subsequently investigated the effect of 1-methoxy-canthin-6-one in combination with human recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in the four cell lines. Suboptimal concentrations (10 micromol/L 1-methoxy-canthin-6-one and 0.25 ng/mL TRAIL, respectively) of the two agents, unable to elicit apoptosis when used alone, induced mitochondrial depolarization, activation of caspase-3, and 45% to 85% of sub-G1 elements when added together to the cells. The synergism seemed to rely partly on the enhanced expression of TRAIL receptor 1 (TRAIL-R1; DR4), analy...Continue Reading

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Citations

Jan 9, 2009·Apoptosis : an International Journal on Programmed Cell Death·Simone Fulda
Nov 23, 2007·Natural Product Reports·Neil DixonJason Micklefield
Oct 22, 2008·Biochemical Pharmacology·Eléonore BeurelChristèle Desbois-Mouthon
May 12, 2007·The International Journal of Biochemistry & Cell Biology·Alessandra RosatiMaria Caterina Turco
Sep 17, 2013·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Manzoor A RatherMushtaq A Qurishi
Apr 20, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiangkun DaiUwe Schneider
Dec 21, 2016·Phytochemical Analysis : PCA·Gerardo Cebrián-TorrejónAlain Fournet
Apr 3, 2020·Phytotherapy Research : PTR·Christian Bailly
Jan 18, 2020·ChemPlusChem·Rafael Dos Santos CostaCristiane Flora Villarreal
Jul 25, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gabriela ChabowskaAnna Wójcicka

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