The potential role of vitamin C in empowering cancer immunotherapy

Bedhiafi, Takwa; Inchakalody, Varghese; Fernandes, Queenie; Mestiri, S; Billa, Nashiru; Uddin, Shahab; Merhi, Maysaloun; Dermime, Said

doi:10.1016/j.biopha.2021.112553

Cited by 31 publications

(18 citation statements)

References 110 publications

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“…It has been shown that antioxidants can enhance the efficacy of immunotherapy via different mechanisms: (i) via a down-regulation of PD-L1 expression in cancer cells, as observed with the antioxidant natural products such as cardamonin, nobiletin, sesamin and hesperetin [ 40 , 41 , 42 , 43 ], (ii) via an upregulation of major histocompatibility complex and surface activation molecules in dendritic cells, as reported with the antioxidant polysaccharide fucoidan [ 44 ], (iii) via the stimulation of TET2 enzyme leading to an increased intratumoral infiltration of T cells and the expression of cytokines and chemokines, as found recently with the prototypical antioxidant ascorbic acid [ 45 ], or (iv) via other mechanisms implicating the HIF1α/STAT3 pathway for example [ 46 ]. Ascorbic acid (vitamin C) has been shown to empower cancer immunotherapy through its pro-oxidant potential, based on its capacity to modulate epigenetic factors and to regulate expression of different cytokines involved in the immune response [ 47 , 48 ]. There are good evidence showing that redox-active treatments can reduce antitumor immunity in part via modulation of the PD-1/PD-L1 checkpoint [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents

et al. 2022

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Small molecules targeting the PD-1/PD-L1 checkpoint are actively searched to complement the anticancer arsenal. Different molecular scaffolds have been reported, including phenyl-pyrazolone derivatives which potently inhibit binding of PD-L1 to PD-1. These molecules are structurally close to antioxidant drug edaravone (EDA) used to treat amyotrophic lateral sclerosis. For this reason, we investigated the capacity of five PD-L1-binding phenyl-pyrazolone compounds (1–5) to scavenge the formation of oxygen free radicals using electron spin resonance spectroscopy with DPPH/DMPO probes. In addition, the reactivity of the compounds toward the oxidized base 5-formyluracil (5fU) was assessed using chromatography coupled to mass spectrometry and photodiode array detectors. The data revealed that the phenyl-pyrazolone derivatives display antioxidant properties and exhibit a variable reactivity toward 5fU. Compound 2 with a N-dichlorophenyl-pyrazolone moiety cumulates the three properties, being a potent PD-L1 binder, a robust antioxidant and an aldehyde-reactive compound. On the opposite, the adamantane derivative 5 is a potent PD-L1 binding with a reduced antioxidant potential and no aldehyde reactivity. The nature of the substituent on the phenyl-pyrazolone core modulates the antioxidant capacity and reactivity toward aromatic aldehydes. The molecular signature of the compound can be adapted at will, to confer additional properties to these PD-L1 binders.

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Section: Discussionmentioning

confidence: 99%

Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents

et al. 2022

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“…Moreover, vitamin C intake below the recommended allowance leads to increased DNA oxidative damage, whereas the consumption of high-dose vitamin C can kill cancer cells [ 272 , 273 ]. Several mechanisms have been proposed to illustrate the anticancer effects of high-dose vitamin C, such as induction of ROS accumulation, epigenetic reprogramming, enhanced immunotherapy efficacy, and inhibition of HIF1 α -induced hypoxia adaptation [ 272 , 274 , 275 ].…”

Section: Antioxidants and Anti-inflammatory Agents In Tumor Therapymentioning

confidence: 99%

Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development

Long

et al. 2022

Oxidative Medicine and Cellular Longevity

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According to numerous animal studies, adverse environmental stimuli, including physical, chemical, and biological factors, can cause low-grade chronic inflammation and subsequent tumor development. Human epidemiological evidence has confirmed the close relationship between chronic inflammation and tumorigenesis. However, the mechanisms driving the development of persistent inflammation toward tumorigenesis remain unclear. In this study, we assess the potential role of reactive oxygen species (ROS) and associated mechanisms in modulating inflammation-induced tumorigenesis. Recent reports have emphasized the cross-talk between oxidative stress and inflammation in many pathological processes. Exposure to carcinogenic environmental hazards may lead to oxidative damage, which further stimulates the infiltration of various types of inflammatory cells. In turn, increased cytokine and chemokine release from inflammatory cells promotes ROS production in chronic lesions, even in the absence of hazardous stimuli. Moreover, ROS not only cause DNA damage but also participate in cell proliferation, differentiation, and apoptosis by modulating several transcription factors and signaling pathways. We summarize how changes in the redox state can trigger the development of chronic inflammatory lesions into tumors. Generally, cancer cells require an appropriate inflammatory microenvironment to support their growth, spread, and metastasis, and ROS may provide the necessary catalyst for inflammation-driven cancer. In conclusion, ROS bridge the gap between chronic inflammation and tumor development; therefore, targeting ROS and inflammation represents a new avenue for the prevention and treatment of cancer.

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“…Vitamin C, also known as ascorbic acid ( Figure 4 ), is a powerful molecule with pleiotropic functions. It has been demonstrated to perform an essential role in immune function; it shows antioxidant, antiviral, anticancer, and antithrombotic effects [ 76 ]. It is mostly represented in the plant world (spinach, chard, broccoli, sweet potatoes, cauliflower, pepper, carrots, peppers, and others) [ 77 , 78 ].…”

Section: Nutraceuticals and Dietary Supplements Against Covid-19 Dise...mentioning

confidence: 99%

Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?

Catalano

Iacopetta

Ceramella

et al. 2022

Foods

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The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID-19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID-19 led to increasing importance of a new disease called post-COVID syndrome. The term post-COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID-19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID-19 disease and post-COVID syndrome.

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The potential role of vitamin C in empowering cancer immunotherapy

Cited by 31 publications

References 110 publications

Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents

Antioxidant Properties and Aldehyde Reactivity of PD-L1 Targeted Aryl-Pyrazolone Anticancer Agents

Reactive Oxygen Species Bridge the Gap between Chronic Inflammation and Tumor Development

Are Nutraceuticals Effective in COVID-19 and Post-COVID Prevention and Treatment?

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