Small molecules regulating reactive oxygen species homeostasis for cancer therapy
Abstract
Elevated intracellular reactive oxygen species (ROS) and antioxidant defense systems have been recognized as one of the hallmarks of cancer cells. Compared with normal cells, cancer cells exhibit increased ROS to maintain their malignant phenotypes and are more dependent on the “redox adaptation” mechanism. Thus, there are two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to prevent or treat cancer. The first strategy, that is, chemoprevention, is to prevent or reduce intracellular ROS either by suppressing ROS production pathways or by employing antioxidants to enhance ROS clearance, which protects normal cells from malignant transformation and inhibits the early stage of tumorigenesis. The second strategy is the ROS‐mediated anticancer therapy, which stimulates intracellular ROS to a toxicity threshold to activate ROS‐induced cell death pathways. Therefore, targeting the regulation of intracellular ROS‐related pathways by small‐molecule candidates is considered to be a promising treatment for tumors. We herein first briefly introduce the source and regulation of ROS, and then focus on small molecules that regulate ROS‐related pathways and show efficacy in cancer therapy from the perspective of pharmacophores. Finally, we discuss several challenges in developing cancer therapeutic agents based on ROS regulation and propose the direction of future development.
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The greatest negative impact of reactive oxygen species is formed during oxidative phosphorylation in the mitochondrial crests at the end of the aerobic respiration process.
“The greatest negative impact is formed during oxidative phosphorylation in the mitochondrial crests at the end of the aerobic respiration process [111,112,113,114].”
From Multi-Target Mechanisms of Phytochemicals in Alzheimer’s Disease: Effects on Oxidative Stress, Neuroinflammation and Protein Aggregation (2022) · cites this paper as [113]
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- Authors
- Zhang, J., Duan, D., Song, Z., Liu, T., Hou, Y., & Fang, J.
- Affiliations
- State Key Laboratory of Applied Organic Chemistry (CN)
- Baoji University of Arts and Sciences (CN)
- Corresponding author
- Fang, Jianguo
- Venue
- Medicinal Research Reviews
- Publisher
- Wiley
- Published
- 2020-09-27
- Volume
- 41
- Issue
- 1
- Pages
- 342-394
- ISSN
- 0198-6325 (ISSN-L)
- 1098-1128
- OpenAlex
- W3089284011
- Cited by
- 184
- References
- 439
- Citations by year
- 2026: 19 · 2025: 29 · 2024: 36 · 2023: 36 · 2022: 37 · 2021: 24 · 2020: 3
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medicinal Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Lanzhou University Institutional Repository (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Keywords
- reactive oxygen species, cancer therapy, redox adaptation, chemoprevention, antioxidants, small molecule drugs, pharmacophore, antioxidant defense, anticancer drug development
- MeSH terms
- Antioxidants, Homeostasis, Humans, Neoplasms, Oxidation-Reduction, Reactive Oxygen Species
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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