A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lipophilic cationic compounds

Kalyanaraman, Balaraman; Cheng, Gang; Hardy, Micaël; Ouari, Olivier; López, Marcos; Joseph, Joy; Zielonka, Jacek; Dwinell, Michael B.

doi:10.1016/j.redox.2017.09.020

Cited by 172 publications

(133 citation statements)

References 95 publications

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“…Infinite proliferation is one of the most prominent characteristics in cancer, and material, such as amino acids and carbohydrates, must be doubled to adjust their metabolism. 19 The rapid use of soluble sugars and the fast proliferation always caused a low-glucose environment within the tumor. Fructose is hexoses monosaccharides, and is isomers of glucose.…”

Section: Discussionmentioning

confidence: 99%

<p>GLUT5 increases fructose utilization in ovarian cancer</p>

Jin¹,

Gong²,

Shang³

2019

OTT

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Background: Fructose is one of the most common dietary carbohydrates in the whole world, and recent studies have found that fructose consumption is closely related to the oncogenesis and development of tumors, however, very few studies have focused on the fructose in ovarian cancer. GLUT5 (Glucose transporter type 5), as a specific fructose transporter in mammalian cells, has also been found highly expressed in many cancers. Methods: In this study, we investigated the abilities of proliferation, colony formation, and migration of ovarian cancer cells in fructose medium, and then silenced GLUT5 in ovarian cancer cells to explore the role GLUT5 in fructose metabolism in ovarian cancer. Results: The results showed that the ovarian cancer cells had similar abilities of proliferation and migration in fructose medium and glucose medium, but silencing GLUT5 could significantly inhibit these abilities in fructose medium. Meanwhile, we found that GLUT5 was higher expressed in ovarian cancer tissues, and its expression correlated significantly with tumor malignancy and poor survival of ovarian cancer patients. Furthermore, the results of animal experiments also demonstrated that intake too much fructose could prominently increase tumor volume, and silencing GLUT5 could significantly inhibit tumor proliferation. Conclusion: In conclusion, we demonstrate that ovarian cancer cells could utilize fructose for their growth, and restricting the fructose intake or targeting GLUT5 may be efficacious strategies for ovarian cancer therapy.

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Section: Discussionmentioning

confidence: 99%

<p>GLUT5 increases fructose utilization in ovarian cancer</p>

Jin¹,

Gong²,

Shang³

2019

OTT

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“…Diseases involving mitochondrial dysfunction can be broadly divided into two groups: diseases that arise from a direct primary mitochondrial cause, typically mutations directly affecting the activity or expression of mitochondrial proteins, and those that originate elsewhere but have effects on the mitochondria. Primary mitochondrial diseases in humans cause a range of diverse outcomes including myopathy, diabetes, kidney disease, epilepsy, autism, blindness, deafness, heart disease, and cancer (Kalyanaraman et al, 2018). Diseases of nonmitochondrial origin that involve mitochondrial dysfunction include many neurodegenerative and neurological disorders such as retinitis pigmentosa, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis (Onyango et al, 2017, Park et al, 2006, Reddy and Beal, 2005.…”

Section: Mitochondrial Disease Modelling In Dictyostelium Mitochondrimentioning

confidence: 99%

The Dictyostelium model for mitochondrial biology and disease

Pearce¹,

Annesley²,

Fisher³

2019

Int. J. Dev. Biol.

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The unicellular slime mould Dictyostelium discoideum is a valuable eukaryotic model organism in the study of mitochondrial biology and disease. As a member of the Amoebozoa, a sister clade to the animals and fungi, Dictyostelium mitochondrial biology shares commonalities with these organisms, but also exhibits some features of plants. As such it has made significant contributions to the study of eukaryotic mitochondrial biology. This review provides an overview of the advances in mitochondrial biology made by the study of Dictyostelium and examines several examples where Dictyostelium has and will contribute to the understanding of mitochondrial disease. The study of Dictyostelium's mitochondrial biology has contributed to the understanding of mitochondrial genetics, transcription, protein import, respiration, morphology and trafficking, and the role of mitochondria in cellular differentiation. Dictyostelium is also proving to be a versatile model organism in the study both of classical mitochondrial disease e.g. Leigh syndrome, and in mitochondria-associated neurodegenerative diseases like Parkinson's disease. The study of mitochondrial diseases presents a unique challenge due to the cryptic nature of their genotypephenotype relationship. The use of Dictyostelium can contribute to resolving this problem by providing a genetically tractable, haploid eukaryotic organism with a suite of readily characterised phenotype readouts of cellular signalling pathways. Dictyostelium has provided insight into the signalling pathways involved in multiple neurodegenerative diseases and will continue to provide a significant contribution to the understanding of mitochondrial biology and disease.

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“…The anticancer activity of the n-hexane extract was attributed to high sterol content. Their selectivity may be related to inhibition of the mitochondrial complex I, which according to Kalyanaraman et al (2018), lipophilic compounds may be a class of therapeutic drugs that inhibit mitochondrial bioenergetics, mitochondrial respiration in tumor cells at relatively non-toxic concentrations. These experiments suggest that the PSC-hex promotes its cytotoxicity by inhibiting tumor-associated signaling pathways.…”

Section: Psc Extract Exhibited Anti-proliferative Activity Against Thmentioning

confidence: 99%

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

Finimundy

Abreu

Bonetto

et al. 2018

Food and Chemical Toxicology

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Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements, presenting antitumor properties through induction of cell death pathways. The PSC potential against colorectal cancer was analyzed by exposing HCT116 cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC value 0.05 mg/mL). The observed cytotoxicity was then associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was able to induce apoptosis related to breakdown of mitochondrial membrane potential and ROS generation. The absence of cytotoxicity in HTC116 and HTC116 cells, alongside with an increase in p53, Bax and Caspase-3 expression, and decrease in Bcl-2 expression, supports that the pro-apoptotic effect is probably induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at G2/M in HCT116 without cytotoxicity in HTC116 cells. These findings suggest that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds present on PSC-hex. Identification of the major components was then performed with ergosta-5,7,22-trien-3β-ol representing 30.6% of total weight. In silico docking studies of ergosta-5,7,22-trien-3β against Bcl-2 were performed and results show a credible interaction with the Bcl-2 hydrophobic cleft. The results show that PSC-hex can be used as supplementary food for adjuvant therapy in colorectal carcinoma.

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A review of the basics of mitochondrial bioenergetics, metabolism, and related signaling pathways in cancer cells: Therapeutic targeting of tumor mitochondria with lipophilic cationic compounds

Cited by 172 publications

References 95 publications

<p>GLUT5 increases fructose utilization in ovarian cancer</p>

<p>GLUT5 increases fructose utilization in ovarian cancer</p>

The Dictyostelium model for mitochondrial biology and disease

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

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