Vitamin C versus Cancer: Ascorbic Acid Radical and Impairment of Mitochondrial Respiration?

Bakalova, Rumiana; Zhelev, Zhivko; Miller, T.; Aoki, Ichio; Higashi, Tatsuya

doi:10.1155/2020/1504048

Cited by 25 publications

(28 citation statements)

References 91 publications

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“…This can impair the electron flow of the respiratory chain, inducing mitochondrial damage. [ 183 ] Increased DNA damage and interference with glycolysis have also been associated with increased levels of H 2 O 2 . [ 184 ] Novel strategies combine ascorbic acid with other drugs [ 185 ] and nanomaterials [ 186 ] to enhance and potentiate the anticancer effect.…”

Section: Strategies To Hijack Endogenous Bioelectricity Of Cancer Cellsmentioning

confidence: 99%

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

Robinson

Jain

Sherman

et al. 2021

Advanced Therapeutics

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Bioelectronic medicine is a treatment modality that uses electricity to treat disease by altering the body's electrical communication systems. All cells are electrically active, in that they possess bioelectric circuitry generating a resting membrane potential and endogenous electric fields that influence cell functions and communication. There is now an accepted paradigm that cancer is characterized by malfunctions in cells' bioelectrical circuitry. This yields opportunities for bioelectronic medicine as novel treatments for cancer by manipulating its bioelectrical properties. To highlight the possibilities a bioelectrical approach can offer cancer therapy, the relevance of bioelectrical activity in cancer is reviewed and also how such activity can be hijacked in novel treatments. This includes sensing or measuring the electrical activity of cells for diagnostic and prognostic applications, controlling or altering bioelectricity including both ionic and faradaic current processes, and eliciting morphological changes using electric fields. Importantly, key links between cellular ionic and faradaic processes that contribute to cancer phenotypes are presented, which if considered and understood as a whole, can bring broad-reaching improvements to cancer therapy.

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Section: Strategies To Hijack Endogenous Bioelectricity Of Cancer Cellsmentioning

confidence: 99%

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

Robinson

Jain

Sherman

et al. 2021

Advanced Therapeutics

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“…In cells, ascorbic acid exists mostly in reduced form due to the activity of two enzymes: (i) Cyb5R3, which converts semi-DHA to ascorbate by one-electron reduction, and (ii) glutathione peroxidase, which converts DHA to ascorbate by two-electron reduction [ 33 , 41 , 42 ].…”

Section: Introductionmentioning

confidence: 99%

Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant

Bakalova

Semkova

Ivanova

et al. 2020

Oxidative Medicine and Cellular Longevity

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Redox-active substances and their combinations, such as of quinone/ascorbate and in particular menadione/ascorbate (M/A; also named Apatone®), attract attention with their unusual ability to kill cancer cells without affecting the viability of normal cells as well as with the synergistic anticancer effect of both molecules. So far, the primary mechanism of M/A-mediated anticancer effects has not been linked to the mitochondria. The aim of our study was to clarify whether this “combination drug” affects mitochondrial functionality specifically in cancer cells. Studies were conducted on cancer cells (Jurkat, Colon26, and MCF7) and normal cells (normal lymphocytes, FHC, and MCF10A), treated with different concentrations of menadione, ascorbate, and/or their combination (2/200, 3/300, 5/500, 10/1000, and 20/2000 μM/μM of M/A). M/A exhibited highly specific and synergistic suppression on cancer cell growth but without adversely affecting the viability of normal cells at pharmacologically attainable concentrations. In M/A-treated cancer cells, the cytostatic/cytotoxic effect is accompanied by (i) extremely high production of mitochondrial superoxide (up to 15-fold over the control level), (ii) a significant decrease of mitochondrial membrane potential, (iii) a decrease of the steady-state levels of ATP, succinate, NADH, and NAD+, and (iv) a decreased expression of programed cell death ligand 1 (PD-L1)—one of the major immune checkpoints. These effects were dose dependent. The inhibition of NQO1 by dicoumarol increased mitochondrial superoxide and sensitized cancer cells to M/A. In normal cells, M/A induced relatively low and dose-independent increase of mitochondrial superoxide and mild oxidative stress, which seems to be well tolerated. These data suggest that all anticancer effects of M/A result from a specific mechanism, tightly connected to the mitochondria of cancer cells. At low/tolerable doses of M/A (1/100-3/300 μM/μM) attainable in cancer by oral and parenteral administration, M/A sensitized cancer cells to conventional anticancer drugs, exhibiting synergistic or additive cytotoxicity accompanied by impressive induction of apoptosis. Combinations of M/A with 13 anticancer drugs were investigated (ABT-737, barasertib, bleomycin, BEZ-235, bortezomib, cisplatin, everolimus, lomustine, lonafarnib, MG-132, MLN-2238, palbociclib, and PI-103). Low/tolerable doses of M/A did not induce irreversible cytotoxicity in cancer cells but did cause irreversible metabolic changes, including: (i) a decrease of succinate and NADH, (ii) depolarization of the mitochondrial membrane, and (iii) overproduction of superoxide in the mitochondria of cancer cells only. In addition, M/A suppressed tumor growth in vivo after oral administration in mice with melanoma and the drug downregulated PD-L1 in melanoma cells. Experimental data suggest a great potential for beneficial anticancer effects of M/A through increasing the sensitivity of cancer cells to conventional anticancer therapy, as well as to the immune system, while sparing normal cells. We hypothesize that M/A-mediated anticancer effects are triggered by redox cycling of both substances, specifically within dysfunctional mitochondria. M/A may also have a beneficial effect on the immune system, making cancer cells “visible” and more vulnerable to the native immune response.

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“…Natural oils were established to boost K concentration [ 59 ], which may boost the chloroplast number/cell, cells per leaf, and accordingly leaf area [ 60 ]. Additionally, natural oils enhanced the antioxidant capacity of treated plants that nullified ROS and maintained chlorophyll functions and stability [ 61 ]. Finally, EO or FO stimulated the carotenoids assimilation and accumulation ( Table 3 ) that defend chlorophyll from oxidation and lastly amplified chlorophyll concentration as recorded in the existing research.…”

Section: Resultsmentioning

confidence: 99%

Acaricidal Efficacy of Jasmine and Lavender Essential Oil or Mustard Fixed Oil against Two-Spotted Spider Mite and Their Impact on Growth and Yield of Eggplants

Farouk

Almutairi²,

Alharbi³

et al. 2021

Biology

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Eggplant is repeatedly attacked by numerous pests, particularly two-spotted spider mite (TSSM), which considerably decline plant productivity. Synthetic acaricides are frequently applied for controlling TSSM, resulting in environmental pollution. The utilization of rational novel substances which repel or prevent TSSM establishment represents a sustainable eco-friendly to reduce the utilization of agrochemicals. A greenhouse investigation was done for assessing the bio-acaricidal activity of mustard (Brassica juncea L.) fixed oil (MFO), jasmine (Jasminum grandiflorum L.) essential oil (JEO), or lavender (Lavandula angustifolia L.) essential oil (LEO), and their influences on eggplant growth and productivity. The results demonstrated that JEO represents the most acaricidal properties against TSSM followed by MFO and/or LEO compared to control. Spraying with natural oils significantly improved eggplant growth, i.e., plant height, number of leaves, and branches/plant, in addition to the leaf area and relative leaf dry mass of the 3rd–5th upper leaves. The JEO had the strongest positive effect compared with other oils or control. Additionally, Natural oils application significantly increased photosynthetic pigment, chlorophyll a:b ratio, and nitrogen, phosphorus, potassium, ascorbic acid, and phenols. The application of oils increased yield and its quality. In this study, JEO (2.5 mL/l) is shown to be extremely promising for the progress of new eco-friendly acaricides, improving plant growth and increasing eggplant yield.

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Vitamin C versus Cancer: Ascorbic Acid Radical and Impairment of Mitochondrial Respiration?

Cited by 25 publications

References 91 publications

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant

Acaricidal Efficacy of Jasmine and Lavender Essential Oil or Mustard Fixed Oil against Two-Spotted Spider Mite and Their Impact on Growth and Yield of Eggplants

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