Interaction of benzoquinones with mitochondria interferes with oxidative phosphorylation characteristics

Makawiti, D.W.; Konji, Victor N.; Olowookere, Julius O.

doi:10.1016/0014-5793(90)81497-c

Cited by 27 publications

(12 citation statements)

References 12 publications

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“…However, previous biochemical studies have shown that benzoquinones including embelin can act as uncouplers of the mitochondrial membrane potential (MMP; Makawiti et al , ). We therefore measured changes in the MMP in response to increasing embelin concentrations and found that proliferating ECs were readily depolarized by low concentrations of embelin, whereas quiescent ECs and tumor cells were not readily uncoupled (Fig A and B and ).…”

Section: Resultsmentioning

confidence: 99%

Embelin inhibits endothelial mitochondrial respiration and impairs neoangiogenesis during tumor growth and wound healing

et al. 2014

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In the normal quiescent vasculature, only 0.01% of endothelial cells (ECs) are proliferating. However, this proportion increases dramatically following the angiogenic switch during tumor growth or wound healing. Recent evidence suggests that this angiogenic switch is accompanied by a metabolic switch. Here, we show that proliferating ECs increasingly depend on mitochondrial oxidative phosphorylation (OxPhos) for their increased energy demand. Under growth conditions, ECs consume three times more oxygen than quiescent ECs and work close to their respiratory limit. The increased utilization of the proton motif force leads to a reduced mitochondrial membrane potential in proliferating ECs and sensitizes to mitochondrial uncoupling. The benzoquinone embelin is a weak mitochondrial uncoupler that prevents neoangiogenesis during tumor growth and wound healing by exhausting the low respiratory reserve of proliferating ECs without adversely affecting quiescent ECs. We demonstrate that this can be exploited therapeutically by attenuating tumor growth in syngenic and xenograft mouse models. This novel metabolic targeting approach might be clinically valuable in controlling pathological neoangiogenesis while sparing normal vasculature and complementing cytostatic drugs in cancer treatment.

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Section: Resultsmentioning

confidence: 99%

Embelin inhibits endothelial mitochondrial respiration and impairs neoangiogenesis during tumor growth and wound healing

et al. 2014

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“…However, earlier investigations reported that maesanin possesses non-specific host defense stimulatory and anti-5-LO activities (Kubo et al, 1987;Fukuyama et al, 1993), and it also inhibits the mitochondrial oxidative phosphorylation (Makawiti et al, 1990). In addition, recent investigations have reported on the antiviral, haemolytic and molluscicidal activities of triterpenoid saponins, isolated from leaves of this plant 2001).…”

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confidence: 97%

Cytotoxic and antioxidant activities of alkylated benzoquinones from Maesa lanceolata

Muhammad

Takamatsu

Walker

et al. 2003

Phytotherapy Research

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The natural and semi-synthetic analogs of substituted 1,4-benzoquinones were evaluated for in vitro cytotoxic and antioxidant activities. Maesanin, dihydromaesanin, maesanin dimethyl ether and isomeric mixtures of 3-[(Z)-10'-pentadecenyl]-benzoquinone derivatives exhibited cytotoxic activity against HL-60 cell line (IC50 values 4.5, 2.2, 0.43 and 2.8 microg/mL, respectively), while it was found to be inactive against ROS (Reactive Oxygen Species) generation in HL-60. In contrast, the isomeric acylated benzoquinones with shorter alkyl substituents, namely, 2-acetoxy-5-hydoxy-6-methyl-3-tridecyl-1,4-benzoquinone and 2-hydoxy-5-acetoxy-6-methyl-3-tridecyl-1,4-benzoquinone showed most prominent antioxidant and antiproliferative effect on HL-60 (IC50 values 6.2 and 2.2 microg/mL, respectively), as well as cytotoxicities against SK-MEL, KB, BT-549 and SK-OV-3 carcinomas (IC50 values <1.1-4.2 microg/mL). All benzoquinones were found to be inactive against cell aggregation and cell adhesion assays, thus showing no effect on immune responses and inflammation.

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“…Because these plant-derived compounds have antibacterial, antifungal, and antiamoebic properties, they are of potential pharmacological use (1). The eventual application of any compound, however, depends on the results of toxicological tests performed to evaluate possible deleterious effects on host organisms as well as on the environment.…”

Section: Introductionmentioning

confidence: 99%

“…Studies with isolated rat liver mitochondria indicate that some benzoquinones (e.g., maesanin) inhibit respiration and that others (e.g., MAQ, embelin, and juglone) potently uncouple mitochondrial electron transfer from phosphorylation (1,3). Makawiti et al (1) have suggested that the uncoupling effect of MAQ and embelin in rat liver may account for the observed inhibition of respiration in cow pea. Such an explanation is not intuitively obvious, however, and we have therefore studied the effect of one of these compounds (MAQ) on respiration in plant mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Maesaquinone: A Novel Inhibitor of Plant Mitochondrial Respiratory Enzymes That React with Ubiquinone

2000

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SummaryThe effect of maesaquinone, 2-(14-nonadecenyl)-3,6-dihydroxy-5-methyl-1,4-benzoquinone, on plant mitochondrial respiration has been investigated. In mitochondria isolated from thermogenic Arum maculatum spadices, this compound inhibits both cytochrome and alternative pathway activities. Kinetic analyses reveal that this inhibition is the result of potent effects of maesaquinone on the alternative oxidase (ID 50 < 0.3 µ M) and complex III (ID 50 < 5 µ M). Succinate dehydrogenase and external NADH dehydrogenase are also inhibited, albeit to a lesser extent (» 30% at 1 µ M). These data suggest that maesaquinone speci cally affects the interaction of the respective enzymes with ubiquinone. IUBMB Life, 49: 533 -537, 2000

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Interaction of benzoquinones with mitochondria interferes with oxidative phosphorylation characteristics

Cited by 27 publications

References 12 publications

Embelin inhibits endothelial mitochondrial respiration and impairs neoangiogenesis during tumor growth and wound healing

Embelin inhibits endothelial mitochondrial respiration and impairs neoangiogenesis during tumor growth and wound healing

Cytotoxic and antioxidant activities of alkylated benzoquinones from Maesa lanceolata

Maesaquinone: A Novel Inhibitor of Plant Mitochondrial Respiratory Enzymes That React with Ubiquinone

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