Antioxidants and Hypoxia in Cancer Therapy

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (5 July 2023) | Viewed by 2108

Special Issue Editor

Special Issue Information

Dear Colleagues,

In order to stop free radicals from causing harm, antioxidants interact with them and neutralize them. Another name for antioxidants is “free radical scavengers”. Some of the antioxidants that the body uses to combat free radicals are produced by it. Endogenous antioxidants is the name given to these compounds. However, the body must obtain the remaining antioxidants it requires from external (exogenous) sources, primarily through diet. Antioxidants appear to be able to: I) reduce the risk of cancer formation by squelching ROS involved in cancer initiation and progression; and II) help cancer and precancer cells to survive once the malignant transformation has already taken place. Antioxidants have been shown to help cancer to develop, hinder cancer treatment by lowering patient survival rates, and vice versa. However, there are also reports of antioxidants having a positive impact on cancer treatment.

Cancer hypoxia, which is acknowledged as one of the most significant characteristics of cancer, affects processes related to metabolism, gene expression, and ultimately tumor biology. Deficient or improper vascularization, as well as systemic hypoxia of the patient (often brought on by anemia), are the main causes of cancer hypoxia. Hypoxia-induced transcription factors then cause a special type of genetic reprogramming (HIF). However, independent of oxygen supply, constitutive activation of oncogene-driven signaling pathways may also activate hypoxia signaling. The angiogenic phenotype, a novel metabolic profile, and the immunosuppressive microenvironment are the results of HIF activation in tumors. Two of the main causes of therapy resistance are cancer hypoxia and the induced adaptation mechanisms. It is clear that cancer patients have an unmet need for targeted hypoxia therapies to enhance the effectiveness of various anticancer therapeutic modalities. Due to the recent approval of the first-in-class HIF2 inhibitor, the case has been opened. The hypoxia inducible transcription factors HIF1a, HIF2a, and HIF3a serve as the central node where hypoxia signaling converges. On the basis of research on various hereditary cancer syndromes, a role for HIFa proteins, particularly HIF1a and HIF2a, in the beginning of tumor formation has also been proposed. There is now a great deal of interest in HIF targeting as a new cancer therapy option. Now, it is time to study the role of antioxidants in cancer hypoxia for cancer treatment.

Prof. Dr. Bonglee Kim
Guest Editor

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Keywords

  • antioxidants
  • hypoxia
  • HIF1alpha
  • HIF2alphfa
  • metastasis
  • cancer
  • Natural products
  • Botanical drugs
  • Drug resistance
  • Apoptosis
  • microRNA

Published Papers (1 paper)

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Research

14 pages, 19342 KiB  
Article
Influence of 2-Nitroimidazoles in the Response of FaDu Cells to Ionizing Radiation and Hypoxia/Reoxygenation Stress
by Faisal Bin Rashed, Wisdom Deebeke Kate, Mesfin Fanta, Leonard Irving Wiebe, Piyush Kumar and Michael Weinfeld
Antioxidants 2023, 12(2), 389; https://doi.org/10.3390/antiox12020389 - 06 Feb 2023
Cited by 1 | Viewed by 1557
Abstract
Cellular adaptations to hypoxia promote resistance to ionizing radiation (IR). This presents a challenge for treatment of head and neck cancer (HNC) that relies heavily on radiotherapy. Standard radiosensitizers often fail to reach diffusion-restricted hypoxic cells, whereas nitroimidazoles (NIs) [such as iodoazomycin arabinofuranoside [...] Read more.
Cellular adaptations to hypoxia promote resistance to ionizing radiation (IR). This presents a challenge for treatment of head and neck cancer (HNC) that relies heavily on radiotherapy. Standard radiosensitizers often fail to reach diffusion-restricted hypoxic cells, whereas nitroimidazoles (NIs) [such as iodoazomycin arabinofuranoside (IAZA) and fluoroazomycin arabinofuranoside (FAZA)] can preferentially accumulate in hypoxic tumours. Here, we explored if the hypoxia-selective uptake of IAZA and FAZA could be harnessed to make HNC cells (FaDu) susceptible to radiation therapy. Cellular response to treatment was assessed through clonogenic survival assays and by monitoring DNA damage (immunofluorescence staining of DNA damage markers, γ-H2AX and p-53BP1, and by alkaline comet assay). The effects of reoxygenation were studied using the following assays: estimation of nucleoside incorporation to assess DNA synthesis rates, immunofluorescent imaging of chromatin-associated replication protein A as a marker of replication stress, and quantification of reactive oxygen species (ROS). Both IAZA and FAZA sensitized hypoxic HNC cells to IR, albeit the former is a better radiosensitizer. Radiosensitization by these compounds was restricted only to hypoxic cells, with no visible effects under normoxia. IAZA and FAZA impaired cellular adaptation to reoxygenation; high levels of ROS, reduced DNA synthesis capacity, and signs of replication stress were observed in reoxygenated cells. Overall, our data highlight the therapeutic potentials of IAZA and FAZA for targeting hypoxic HNC cells and provide rationale for future preclinical studies. Full article
(This article belongs to the Special Issue Antioxidants and Hypoxia in Cancer Therapy)
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