Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer

Tomasetti, Marco; Santarelli, Lory; Alleva, Renata; Dong, Lan-Feng; Neužil, Jiřı́

doi:10.2174/0929867321666140915142219

Cited by 20 publications

(17 citation statements)

References 182 publications

(232 reference statements)

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“…It was therefore speculated that an exogenous increase of ROS stress in cancer cells causes an elevation of intracellular ROS above a toxic threshold by overwhelming the antioxidant capacity of the cell. This provides a mechanistic basis to apply pro-oxidative therapeutic strategies (such as high-dose ascorbate) to kill cancer cells using ROS-mediated mechanisms [18,19]. Thus, it seems plausible to assume that increasing ROS (superoxide) production and the labile iron pool in cancer cells may sensitize them to ascorbate [20]; however, extracellular iron at physiological conditions may also diminish the anticancer effects of ascorbate [21].…”

Section: Historical Backgroundmentioning

confidence: 99%

Molecular mechanisms of pharmacological doses of ascorbate on cancer cells

Venturelli

Sinnberg

Niessner

et al. 2015

Wien Med Wochenschr

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Intravenous application of high-dose ascorbate (vitamin C) has been used in complementary medicine since the 1970s to treat cancer patients. In recent years it became evident that high-dose ascorbate in the millimolar range bears selective cytotoxic effects on cancer cells in vitro and in vivo. This anticancer effect is dose dependent, catalyzed by serum components and mediated by reactive oxygen species and ascorbyl radicals, making ascorbate a pro-oxidative pro-drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. It further depends on HIF-1 signaling and oxygen pressure, and shows a strong epigenetic signature (alteration of DNA-methylation and induction of tumor-suppressing microRNAs in cancer cells). The detailed understanding of ascorbate-induced antiproliferative molecular mechanisms warrants in-depth preclinical evaluation in cancer-bearing animal models for the optimization of an efficacious therapy regimen (e.g., combination with hyperbaric oxygen or O2-sensitizers) that subsequently need to be evaluated in clinical trials.

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Section: Historical Backgroundmentioning

confidence: 99%

Molecular mechanisms of pharmacological doses of ascorbate on cancer cells

Venturelli

Sinnberg

Niessner

et al. 2015

Wien Med Wochenschr

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“…Synthetic α-TP derivative such as α-tocopherol succinate (α-TS) is known as a compound inducing apoptosis of cells of various origin. Pro-apoptotic effect of α-TS is well studied in cancer cell cultures mainly due to the works of J. Neuzil et al [23] that found the basis for the use of this compound as an antitumor agent. There are numerous and varied assumed mechanisms of α-TS action [24,25].…”

Section: Resultsmentioning

confidence: 99%

The sensitivity of cells with the various level of NAD(P)H:quinone oxidoreductase 1

Parshykov¹

2015

Ukr.Biochem.J.

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The effects of α-tocopherol with shortened to 6 carbon atoms side chain ), α-tocopherol succinate (α-Ts) and quinonimine 2,6-dichlorophenolindophenol (DCPIP) on DT-diaphorase activity and viability of rat thymocytes, splenocytes and hepatocytes were investigated. It was shown that the lowest basal activity of the enzyme is inherent in splenocytes. In comparison to splenocytes, DT-diaphorase activity was 1.4 and 5 times higher in thymocytes and hepatocytes, respectively. It was found that the sensitivity of cells to the cytotoxic effect of DCPIP was inversely proportional to the basal level of DT-diaphorase activity and accompanied by its activation with subsequent inhibition at non-toxic and toxic concentrations, respectively. hepatocytes were least sensitive to the cytotoxic effect of α-Toc-C 6 . In thymocytes and splenocytes α-Toc-C 6 exerts inhibitory effects on DT-diaphorase, whereas in hepatocytes an increased activity of the enzyme was observed, which probably caused their high survival rate. simultaneous induction of cytochrome P450 enzyme expression by α-Toc-C 6 in hepatocytes is also possible. Cytotoxic effect of α-Ts does not depend on the basal level of DT-diaphorase activity in cells, is not accompanied by its induction and it is most likely determined by the non-specific esterase activity. k e y w o r d s: α-tocopherol with shortened to 6 carbon atoms side chain (α-Toc-C 6 ), α-tocopherol succinate (α-Ts), quinonimines, thymocytes, splenocytes, hepatocytes, DT-diaphorase.

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“…the formation of the superoxide radical anion (O2 •-) and hydrogen peroxide (H2O2), respectively. These species represent aggressive reactive oxygen species (ROS) which can cause serious damage to cells, and often induce apoptosis via the oxidation of redox sensitive proteins and enzymes and the subsequent activation of one of the pro-apoptotic pathways (Tomasetti, 2015). Depending on the precise chemical structure, quinones are also able to act as electrophiles in Michael addition reactions.…”

Section: The Biological Chemistry Of Active Ingredientsmentioning

confidence: 99%

Togo to go: Products and compounds derived from local plants for the treatment of diseases endemic in Sub-Saharan Africa

Tittikpina

Ejike

Estevam

et al. 2017

Afr. J. Trad. Compl. Alt. Med.

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TOGO TO GO: PRODUCTS AND COMPOUNDS DERIVED FROM LOCAL PLANTS FOR THE TREATMENT OF DISEASES ENDEMIC IN SUB-SAHARAN AFRICA AbstractBackground: Many African countries suffer from endemic diseases which are often caused by infections and seriously affect the social and economic development of these nations. While the access to proper medication is still limited, many of these countries are, at the same time, rich in medical plants. Materials and Methods:A review of relevant scientific (and gray) literature was carried out and information obtained from local authorities in medicinal plants. A synthesis of the data obtained was thereafter performed and recommendations for the future proposed.Results: Plants such as Cissus aralioides, Securidaca longipedunculata, Piliostigma thonningii, Nauclea latifolia, Ocimum gratissimum and Newbouldia laevis are widely reported to be used in the treatment of endemic diseases in Togo and her neighbouring countries.These plants often contain highly potent chemical compounds, such as quinones, xanthones, tannins and terpenes and therefore may provide an alternative avenue to short-term treatment. A combination of further analysis of plant materials and their active ingredients on the one hand, and modern technology to turn such natural products into commercial equivalents on the other, is required in order to identify the targets and modes of action of these natural materials, unlock access to them, and ultimately produce valuable medicines and phytoprotectants based on locally grown plant materials. Conclusion:The production of plant-derived products, as advocated in this paper, is in line with the WHO's traditional medicine strategy 2014-2023, and will eventually yield a sustainable health-and-wealth generating cycle that will benefit a countries in the region, economically and ecologically.Keywords: Togo, redox active secondary metabolites, phytochemicals, antimalarial activity, antidiarrheal activity, tropical diseases. Plants as a widely used natural resource in TogoMany sub-Saharan African countries suffer from immense health-related problems, diseases and epidemics, which impact heavily on their populations, and hold back the development of their societies and economies. This issue has recently been highlighted by the outbreak of Ebola, yet there are also many other, equally damaging diseases, including, for instance, malaria, various types of fevers and infections by bacteria and infestations by pathogenic nematodes (Hotez and Kamath, 2009;Crump, 2012). Paradoxically, whilst these countries are a hotbed of infectious diseases, they are also rich in natural resources, and among them a myriad of plants containing biologically active ingredients which seem to be active against many microbes. By unlocking this treasure chest of local "green gold", it should therefore, in theory, eventually be possible to develop affordable medicines locally and to apply them to the populations in need. Since many of these natural products are also active against agricultural pests (Shrivatava et a...

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Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer

Cited by 20 publications

References 182 publications

Molecular mechanisms of pharmacological doses of ascorbate on cancer cells

Molecular mechanisms of pharmacological doses of ascorbate on cancer cells

The sensitivity of cells with the various level of NAD(P)H:quinone oxidoreductase 1

Togo to go: Products and compounds derived from local plants for the treatment of diseases endemic in Sub-Saharan Africa

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