The awakening of an advanced malignant cancer: An insult to the mitochondrial genome

Cook, Cody C.; Higuchi, Masahiro

doi:10.1016/j.bbagen.2011.08.017

Cited by 29 publications

(29 citation statements)

References 204 publications

(247 reference statements)

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“…Mitochondrial respiration could be affected by a variety of changes in mitochondrial genes including those encoding respiratory chain complexes, which are also affected by carcinogenesis [24,25]. We next assessed if the decreased OCR induced by leptin is associated with changes in the gene and protein expression profile of major mitochondrial proteins.…”

Section: Resultsmentioning

confidence: 99%

Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

et al. 2013

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Obesity is a key risk factor for the development of colon cancer; however, the endocrine/paracrine/metabolic networks mediating this connection are poorly understood. Here we hypothesize that obesity results in secreted products from adipose tissue that induce malignancy-related metabolic alterations in colon cancer cells. Human HCT116 colon cancer cells, were exposed to conditioned media from cultured human adipose tissue fragments of obese vs. non-obese subjects. Oxygen consumption rate (OCR, mostly mitochondrial respiration) and extracellular acidification rate (ECAR, mostly lactate production via glycolysis) were examined vis-à-vis cell viability and expression of related genes and proteins. Our results show that conditioned media from obese (vs. non-obese) subjects decreased basal (40%, p<0.05) and maximal (50%, p<0.05) OCR and gene expression of mitochondrial proteins and Bax without affecting cell viability or expression of glycolytic enzymes. Similar changes could be recapitulated by incubating cells with leptin, whereas, leptin-receptor specific antagonist inhibited the reduced OCR induced by conditioned media from obese subjects. We conclude that secreted products from the adipose tissue of obese subjects inhibit mitochondrial respiration and function in HCT116 colon cancer cells, an effect that is at least partly mediated by leptin. These results highlight a putative novel mechanism for obesity-associated risk of gastrointestinal malignancies, and suggest potential new therapeutic avenues.

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Section: Resultsmentioning

confidence: 99%

Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

et al. 2013

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“…Further, using AD transgenic mice lines, multiple studies found increased production of free radicals, cytochrome c oxidase activity, lipid peroxidation, and reduced levels mitochondrial ATP in affected brain regions [11,19,20,30,34-43,60,61], and primary neurons AD transgenic mice or neurons expressing mutant APP and Aβ [32,47-50], further supporting mitochondrial dysfunction and oxidative stress are important features of AD pathogenesis.…”

Section: Mitochondrial Defects In Alzheimer’s Diseasementioning

confidence: 99%

Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: Implications to mitochondria-targeted antioxidant therapeutics

Reddy

Tripathi

Troung

et al. 2012

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

320

232

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Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer’s disease (AD) progression. Loss of synapses and synaptic damage are the best correlate of cognitive deficits found in AD patients. Recent research on amyloid bet (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed that reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD.

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“…Therefore, measurement of the relative expressions of β-F1-ATPase and glyceraldehyde-3-phosphate dehydrogenase may have prognostic value for breast and other cancers (51). Moreover, mtDNA is reduced in cancer and impaired mitochondrial metabolism may also play a key role in cancer development (52, 53). The mechanism may include increased mitochondrial degradation (mitophagy), lower mitochondrial proliferation, or both (52).…”

Section: Metabolic Reprograming and Crcmentioning

confidence: 99%

Putative Role of Adipose Tissue in Growth and Metabolism of Colon Cancer Cells

Schwartz

Yehuda‐Shnaidman

2014

Front. Oncol.

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Newly emerging data highlight obesity as an important risk factor for developing certain types of cancer, including colorectal cancer. Although evidence supports a link between the two, the mechanisms responsible for this relationship have not yet been fully elucidated. Hypertrophied and dysfunctional adipose tissue of the obese state is characterized by low-grade inflammation. Adipokines and cytokines secreted from adipocytes, together with the abundant availability of lipids from adipocytes in the tumor microenvironment, promote adhesion, migration, and invasion of tumor cells and support tumor progression and uncontrolled growth. One of the predisposed targets of the deleterious effects exerted by secretions from adipose tissue in obesity is the activities associated with the cellular mitochondria. Mitochondrial oxidative metabolism plays a key role in meeting cells’ energetic demands by oxidative phosphorylation (OxPhos). Here we discuss: (a) the dynamic relationship between glycolysis, the tricarboxylic acid cycle, and OxPhos; (b) the evidence for impaired OxPhos (i.e., mitochondrial dysfunction) in colon cancer; (c) the mechanisms by which mitochondrial dysfunction can predispose to cancer. We propose that impaired OxPhos increases susceptibility to colon cancer since OxPhos is sensitive to a large number of factors that are intrinsic to the host (e.g., inflammation). Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes should reveal new therapeutic possibilities.

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The awakening of an advanced malignant cancer: An insult to the mitochondrial genome

Cited by 29 publications

References 204 publications

Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

Secreted Human Adipose Leptin Decreases Mitochondrial Respiration in HCT116 Colon Cancer Cells

Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: Implications to mitochondria-targeted antioxidant therapeutics

Putative Role of Adipose Tissue in Growth and Metabolism of Colon Cancer Cells

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