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Review
. 2020 Jul 6;11(17):5236-5244.
doi: 10.7150/jca.46200. eCollection 2020.

Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

Shuyi Mi  1   2 , Liang Gong  3 , Ziqi Sui  1   4
Affiliations
Review

Friend or Foe? An Unrecognized Role of Uric Acid in Cancer Development and the Potential Anticancer Effects of Uric Acid-lowering Drugs

Shuyi Mi et al. J Cancer. .

Abstract

In recent years, metabolic syndrome (Mets) has been a hot topic among medical scientists. Mets has an intimate relationship with the incidence and development of various cancers. As a contributory factor of Mets, hyperuricemia actually plays an inseparable role in the formation of various metabolic disorders. Although uric acid is classically considered an antioxidant with beneficial effects, mounting evidence indicates that a high serum uric acid (SUA) level may serve as a pro-oxidant to generate inflammatory reactions and oxidative stress. In this review, we describe the unrecognized role of hyperuricemia in cancer development and summarize major mechanisms linking uric acid to carcinogenesis. Furthermore, we also discuss the potential mechanism of liver metastasis of cancer and list some types of uric acid-lowering agents, which may exert anticancer effects.

Keywords: cancer risk; hyperuricemia; liver metastasis; metabolic syndrome; uric acid-lowering agents.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
The progression of cancer and metastasis to the liver during hyperuricemia conditions. During hyperuricemia, the main forms of uric acid are soluble uric acid (sUA) and monosodium urate (MSU) crystals. As one of the damage-associated molecular patterns that alert the immune system to injurious situations, MSU crystals are detected and ingested by phagocytes, which stimulate the NOD-like receptor family and pyrin domain containing 3 (NLRP3) inflammasomes and generate reactive oxygen species (ROS) mainly in intracellular way. NLRP3 inflammasomes then promote cleavage of IL-1β into its active form, thus producing the IL-1β proinflammatory cytokine. Depending on the presence of MSU, sUA also participates in this process. The presence of ROS and IL-1β result in oxidative stress and inflammatory responses, respectively, which promote cancer development. Furthermore, hyperuricemia also alters the microenvironment of the liver, making it more likely that cancer will metastasize.
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