Aspirin metabolites 2,3 ‑DHBA and 2,5‑DHBA inhibit cancer cell growth: Implications in colorectal cancer prevention.

Aspirin metabolites 2,3‑DHBA and 2,5‑DHBA inhibit cancer cell growth: Implications in colorectal cancer prevention. Mol Med Rep. 2019 Nov 18;: Authors: Sankaranarayanan R, Valiveti CK, Dachineni R, Kumar DR, Lick T, Bhat GJ Abstract Although compelling evidence exists on the ability of aspirin to treat colorectal cancer (CRC), and numerous theories and targets have been proposed, a consensus has not been reached regarding its mechanism of action. In this regard, a relatively unexplored area is the role played by aspirin metabolites 2,3‑dihydroxybenzoic acid (2,3‑DHBA) and 2,5‑dihydroxybenzoic acid (2,5‑DHBA) in its chemopreventive actions. In a previous study, we demonstrated that 2,3‑DHBA and 2,5‑DHBA inhibited CDK1 enzyme activity in vitro. The aim of the present study was to understand the effect of these metabolites on the enzyme activity of all CDKs involved in cell cycle regulation (CDKs 1, 2, 4 and 6) as well as their effect on clonal formation in three different cancer cell lines. Additionally, in silico studies were performed to determine the potential sites of interactions of 2,3‑DHBA and 2,5‑DHBA with CDKs. We demonstrated that 2,3‑DHBA and 2,5‑DHBA inhibits CDK‑1 enzyme activity beginning at 500 µM, while CDK2 and CDK4 activity was inhibited only at higher concentrations (>750 µM). 2,3‑DHBA inhibited CDK6 enzyme activity from 250 µM, while 2,5‑DHBA inhibited its activity >750 Â...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research