Cyclooxygenase (COX) is a type of isoenzyme that plays a role in the synthesis of prostaglandins and other prostaglandin like substances (such as thromboxanes) from arachidonic acid. Importantly, COX enzyme catalyzes the conversion of arachidonic acid to prostaglandins. This enzyme has two known isoenzymes, namely cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Particularly, COX-1 enzyme regulates many cellular processes, including platelet aggregation, renal artery dilation, and gastric mucosal acid protection. Obviously, COX-2 enzyme is an inducible enzyme that increases during the inflammatory process. Meanwhile, COX-2 specific NSAID works by preferentially inhibiting COX-2. Nonetheless, COX-2 mediates several of the most important components of mucosal defense and plays a crucial role in regulating ulcer healing. Today, we will introduce a selective COX-2 inhibitor for cancer and acute liver injury research, Acetaminophen.

Acetaminophen is a Selective COX-2 Inhibitor for Cancer and Acute Liver Injury Research.

Above all, Acetaminophen (Paracetamol) is a selective COX-2 inhibitor with an IC50 of 25.8 μM; is a widely used antipyretic and analgesic agent. Acetaminophen is a potent hepatic N-acetyltransferase 2 (NAT2) inhibitor. Acetaminophen induces ferroptosis and leads to acute liver injury in mice model.

Next in importance, MTT assay shows that Acetaminophen (APAP) in a dose of 50 mM significantly reduces cell viability to 61.5±6.65%. Interestingly, the significant increase in cell viability to 79.7% is observed in the Acetaminophen/HV110 co-treated cells, compared to Acetaminophen treated cells.

Once again, administering Acetaminophen to the mice causes significant liver damage and necrosis of cells. Besides, Acetaminophen induces ferroptosis, by enhancing levels of Fe2+ and MDA, and decreasing levels of GSH and GPX4. Moreover, Acetaminophen induces acut eliver injury in C57BL/6J mice model.

All in all, Acetaminophen is a selective COX-2 inhibitor for cancer and acute liver injury research.

References:

Miroslav Dinić, et al. Front Microbiol. 2017 Apr 6;8:594.

Uchida NS, et al. Evid Based Complement Alternat Med. 2017;2017:1796209.