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Open AccessReview

Do Aspirin and Flavonoids Prevent Cancer through a Common Mechanism Involving Hydroxybenzoic Acids?—The Metabolite Hypothesis

1
Department of Pharmaceutical Sciences and Translational Cancer Research Center, South Dakota State University, College of Pharmacy and Allied Health Professions, Brookings, SD 57007, USA
2
Department of Entomology, University of Kentucky, Lexington, KY 40506, USA
*
Author to whom correspondence should be addressed.
Academic Editor: H.P. Vasantha Rupasinghe
Molecules 2020, 25(9), 2243; https://doi.org/10.3390/molecules25092243
Received: 30 March 2020 / Revised: 2 May 2020 / Accepted: 9 May 2020 / Published: 10 May 2020
(This article belongs to the Special Issue Flavonoids and Their Disease Prevention and Treatment Potential)
Despite decades of research to elucidate the cancer preventive mechanisms of aspirin and flavonoids, a consensus has not been reached on their specific modes of action. This inability to accurately pinpoint the mechanism involved is due to the failure to differentiate the primary targets from its associated downstream responses. This review is written in the context of the recent findings on the potential pathways involved in the prevention of colorectal cancers (CRC) by aspirin and flavonoids. Recent reports have demonstrated that the aspirin metabolites 2,3-dihydroxybenzoic acid (2,3-DHBA), 2,5-dihydroxybenzoic acid (2,5-DHBA) and the flavonoid metabolites 2,4,6-trihydroxybenzoic acid (2,4,6-THBA), 3,4-dihydroxybenzoic acid (3,4-DHBA) and 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) were effective in inhibiting cancer cell growth in vitro. Limited in vivo studies also provide evidence that some of these hydroxybenzoic acids (HBAs) inhibit tumor growth in animal models. This raises the possibility that a common pathway involving HBAs may be responsible for the observed cancer preventive actions of aspirin and flavonoids. Since substantial amounts of aspirin and flavonoids are left unabsorbed in the intestinal lumen upon oral consumption, they may be subjected to degradation by the host and bacterial enzymes, generating simpler phenolic acids contributing to the prevention of CRC. Interestingly, these HBAs are also abundantly present in fruits and vegetables. Therefore, we suggest that the HBAs produced through microbial degradation of aspirin and flavonoids or those consumed through the diet may be common mediators of CRC prevention. View Full-Text
Keywords: aspirin; flavonoids; cancer prevention; hydroxybenzoic acids; cell cycle; CDKs; colorectal cancer aspirin; flavonoids; cancer prevention; hydroxybenzoic acids; cell cycle; CDKs; colorectal cancer
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Sankaranarayanan, R.; Kumar, D.R.; Patel, J.; Bhat, G.J. Do Aspirin and Flavonoids Prevent Cancer through a Common Mechanism Involving Hydroxybenzoic Acids?—The Metabolite Hypothesis. Molecules 2020, 25, 2243.

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