Avicins, a novel plant-derived metabolite lowers energy metabolism in tumor cells by targeting the outer mitochondrial membrane

Haridas, Valsala; Li, Xiaoxian; Mizumachi, Takatsugu; Higuchi, Masahiro; Lemeshko, Viktor V.; Colombini, Marco; Gutterman, Jordan U.

doi:10.1016/j.mito.2006.12.005

Cited by 54 publications

(46 citation statements)

References 39 publications

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“…Biophysical studies using lipid bilayers revealed that avicins target and close VDAC. Closure of VDAC would lead to an overall lowering of the cell energy metabolism, subsequently pushing these cells towards the apoptotic pathway by permeabilization of the OMM and release of cytochrome c [101]. This observation, however, is in contrast with the report that hexokinase-I, which binds to VDAC and causes its closure, inhibits cytochrome c release and protects against apoptotic cell death [102].…”

Section: Induction Of Mptmentioning

confidence: 90%

Mitochondria as targets for chemotherapy

2009

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Mitochondrial malfunctioning is implicated in the pathogenesis of a variety of disorders, including cancer and multiple neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. Disturbance of mitochondrial vital functions, e.g., production of ATP, calcium buffering capacity, and generation of reactive oxygen species, can be potentially involved in disease pathogenesis. Neurological disorders caused by mitochondrial deterioration are often associated with cell loss within specific brain regions. In contrast, mitochondrial alterations in tumor cells and the "Warburg effect" might lead to cell survival and resistance of tumor cells to chemotherapy. This review is devoted to the role of mitochondria in neurodegeneration and tumor formation, and describes how targeting of mitochondria can be beneficial in the therapy of these diseases, which affect a large human population.

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Section: Induction Of Mptmentioning

confidence: 90%

Mitochondria as targets for chemotherapy

2009

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“…The first underlined the ability of avicins to induce the outer mitochondrial membrane permeabilisation which leads to decrease respiratory activity (Lemeshko et al 2006). The second demonstrated that avicins reduce the rate of respiration and levels of ATP in Jurkat cells after inhibition of the voltage dependent anion channel in the outer mitochondrial membrane (Haridas et al 2007). This is possibly the main mechanism for apoptosis induction by avicins.…”

Section: Acaciosidesmentioning

confidence: 98%

A review of acacic acid-type saponins from Leguminosae-Mimosoideae as potent cytotoxic and apoptosis inducing agents

et al. 2011

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“…The proapoptotic compound of potential anti-cancer activity, i.e. oblimersen (phosphorothioate antisense oligonucleotide targeted to the initiation codon region of the Bcl-2 mRNA, known also as (G3139), dimethylarsinous acid (DMA III) and methyl jasmonate are known to interact with VDAC as well although in the case of the latter the interference with VDAC-other protein interaction has been shown [85][86][87][88][89][90][91][92][93][94].…”

Section: Vdac As a Therapeutic Targetmentioning

confidence: 99%

VDAC as a Potential Target in Huntingtons Disease Therapy: The State of the Art

Karachitos¹,

Grobys²

2015

Pharmaceut Reg Affairs

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It is becoming increasingly evident that mitochondria dysfunction plays an important role in pathogenesis of Huntington's disease (HD). However, the underlying mechanism is still needs to be explained. The crucial aspect of the explanation is to indicate the upstream events in mitochondria dysfunction that could contribute to HD. In the review we propose the defect of voltage-dependent anion-selective channel (VDAC), as a causative event in HDrelated mitochondria dysfunction. Thus, we propose to consider VDAC as a crucial element in HD etiology and consequently as a reasonable target for therapeutic interventions in HD, based on developing novel therapeutic strategies eliminating mitochondria dysfunction.Keywords: Huntington's disease; VDAC; Mitochondria; Therapy Huntington's DiseaseHuntington's disease (HD) is a progressive and fatal neurodegenerative disease with a prevalence of about 5-10/100 000. Clinically, the disease is characterized by progressive chorea (involuntary dance-like movements), rigidity, weight loss, dementia, seizures and psychiatric disturbances such as depression, withdrawal and irritability. These symptoms including cognitive deterioration, psychiatric disturbances, and movement disorders result from a selective and continuous loss of neurons from the striatum and deep layers of the cerebral cortex although other brain regions such as thalamus and subthalamic nucleus are also affected [1][2][3]. Current treatments for HD relieve merely the symptoms and address the control of behavioral symptoms, motor sedatives, cognitive enhancers, and neuroprotective agents [4,5] but are not able to restore neuronal function nor to stop the insidious loss of neurons. As summarized by Kumar et al. [6], although there is an intensive research concerning development of neuroprotective strategies such as fetal neural transplantation, RNA interference (RNAi) and transglutaminase inhibitors (TGaseI), effective therapeutic strategies may not be developed until the next few decades. Thus, a new therapeutic approach involving new potential targets and to start before the symptomatic stage could contribute to HD treatment to be more specific and effective. This, in turn, requires further studies concerning molecular mechanisms underlying HD.The genetic hallmark of HD is an expansion of an unstable trinucleotide CAG repeat region within the first exon of the gene encoding the protein Huntington (Htt). This results in synthesis of its mutant form (mHtt) containing more than 36 glutamine residues at N terminus although the possible contribution of mHtt encoding mRNA, i.e. toxic mRNA in HD etiology has also been suggested [7]. HD inheritance is autosomal dominant and consequently the prevailing view is that mHtt mediated symptoms result from a toxic gain-offunction mechanism although loss-of-function mechanisms for mHtt and Htt are also proposed [8,9]. Htt is conserved among vertebrates [10], is localized mainly in cytoplasm and exhibits anti-apopptotic properties [11,12]. Importantly, Htt expression in diffe...

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Avicins, a novel plant-derived metabolite lowers energy metabolism in tumor cells by targeting the outer mitochondrial membrane

Cited by 54 publications

References 39 publications

Mitochondria as targets for chemotherapy

Mitochondria as targets for chemotherapy

A review of acacic acid-type saponins from Leguminosae-Mimosoideae as potent cytotoxic and apoptosis inducing agents

VDAC as a Potential Target in Huntingtons Disease Therapy: The State of the Art

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