Denbinobin, a naturally occurring 1,4-phenanthrenequinone, inhibits HIV-1 replication through an NF-κB-dependent pathway

Sánchez‐Duffhues, Gonzalo; Calzado, Marco A.; Vinuesa, Amaya García de; Caballero, Francisco J.; Ech‐Chahad, Abdellah; Appendino, Giovanni; Krohn, Karsten; Fiebich, Bernd L.; Muñóz, Eduardo

doi:10.1016/j.bcp.2008.09.006

Cited by 46 publications

(36 citation statements)

References 57 publications

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“…denbinobin), can trigger apoptosis by generating ROS [34], that in turn should induce mitochondrial membrane disruption. We therefore determined by flow cytometry the levels of the DNA intercalating fluorescent marker ethidium which is produced after intracellular oxidation of DHE.…”

Section: Tq Induces the Generation Of Ros And The Breakdown Of M Inmentioning

confidence: 99%

Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1

Alhosin

Abusnina

Achour

et al. 2010

Biochemical Pharmacology

132

116

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The salvage anti-tumoral pathway which implicates the p53-related p73 gene is not yet fully characterized. We therefore attempted to identify the up-and down-stream events involved in the activation of the p73-dependent pro-apoptotic pathway, by focusing on the anti-apoptotic and epigenetic integrator UHRF1 which is essential for cell cycle progression. For this purpose, we analyzed the effects of a known anti-neoplastic drug, thymoquinone (TQ), on the p53-deficient acute lymphoblastic leukemia (ALL) Jurkat cell line. Our results showed that TQ inhibits the proliferation of Jurkat cells and induces G1 cell cycle arrest in a dose-dependent manner. Moreover, TQ treatment triggers programmed cell death, production of reactive oxygen species (ROS) and alteration of the mitochondrial membrane potential (m). TQ-induced apoptosis, confirmed by the presence of hypodiploid G0/G1 cells, is associated with a rapid and sharp re-expression of p73 and dose-dependent changes of the levels of caspase-3 cleaved subunits. These modifications are accompanied by a dramatic down-regulation of UHRF1 and two of its main partners, namely DNMT1 and HDAC1, which are all involved in the epigenetic code regulation. Knockdown of p73 expression restores UHRF1 expression, reactivates cell cycle progression and inhibits TQ-induced apoptosis. Altogether our results showed that TQ mediates its growth inhibitory effects on ALL p53-mutated cells via the activation of a p73-dependent mitochondrial and cell cycle checkpoint signaling pathway which subsequently targets UHRF1.

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Section: Tq Induces the Generation Of Ros And The Breakdown Of M Inmentioning

confidence: 99%

Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1

Alhosin

Abusnina

Achour

et al. 2010

Biochemical Pharmacology

132

116

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“…1 H and 13 C NMR spectra were recorded with a Bruker Avance 500 MHz spectrometer in CDCl 3 or CDCl 3 /CD 3 OD. Chemical shifts are given relative to TMS (δ = 0 ppm) as internal standard, and coupling constants J are reported in Hz.…”

Section: Methodsmentioning

confidence: 99%

“…[1] Recently, it was discovered by the group of Munoz that denbinobin (1) (Figure 1), a naturally occurring 1,4-phenanthrenequinone, [2] inhibits HIV-1 replication [3] and also induces apoptosis by generation of reactive oxygen species in human leukemic cells. [4] Independently, Lee et al [5] reported on cytotoxic 1,4-phenanthrenequinones from Calanthe arisanensis showing that compound 2 with a phenolic hydroxy group at C-5 [6] had by far the highest cytotoxic activity against a broad panel of human tumor cell lines.…”

Section: Introductionmentioning

confidence: 99%

Novel 1,4,5,8‐Phenanthrenediquinones and Unusual Deoxygenation with Trimethylsilyl Iodide

et al. 2009

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Attempt for aryl methyl ether cleavage of 5,8-dimethoxy-1,4-phenanthrenequinone (4) with boron trichloride or tribromide resulted in the halogenation of the quinone double bond to form 5a,b. Surprisingly, reaction of dimethyl ether 4 with trimethylsilyl iodide afforded the phenanthrenediquinone 6, whereas deoxygenation to 8 and 9 occurred by reaction of trimethylsilyl iodide with derivative 7. The phen-

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“…57 Nas diferentes plantas pesquisadas é muito grande a variedade de compostos isolados com ação anti-HIV, tendo sido encontradas substâncias de várias classes, 57 como taninos (geraniina, 8 e corilagina, 9); flavonoides (baicalina, 14 catequina,17; quercetina, 18), lignanas (taxifolina, 19; kadsurina, 20; interiorina, 21), terpenoides (hemslecina A, 22 e B, 23; ác. ursólico, 24; kuguacinas C, 25 e E, 26; ác.…”

Section: Acer Okamotoanum Nakaiunclassified

HIV: mecanismo de replicação, alvos farmacológicos e inibição por produtos derivados de plantas

Ferreira¹,

Riffel²,

Santana³

2010

Quím. Nova

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Denbinobin, a naturally occurring 1,4-phenanthrenequinone, inhibits HIV-1 replication through an NF-κB-dependent pathway

Cited by 46 publications

References 57 publications

Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1

Induction of apoptosis by thymoquinone in lymphoblastic leukemia Jurkat cells is mediated by a p73-dependent pathway which targets the epigenetic integrator UHRF1

Novel 1,4,5,8‐Phenanthrenediquinones and Unusual Deoxygenation with Trimethylsilyl Iodide

HIV: mecanismo de replicação, alvos farmacológicos e inibição por produtos derivados de plantas

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