Iminodibenzyl redirected cyclooxygenase-2 catalyzed dihomo-γ-linolenic acid peroxidation pattern in lung cancer.

ABSTRACT: Cyclooxygenase-2 (COX-2) is up-regulated by redox imbalance and is considered a target for cancer therapy. The rationale of the COX-2 inhibitor lies in suppressing COX-2 catalyzed peroxidation of omega-6 polyunsaturated fatty acids (PUFAs), which are essential and pervasive in our daily diet. However, COX-2 inhibitors fail to improve cancer patients' survival and may lead to severe side effects. Here, instead of directly inhibiting COX-2, we utilize a small molecule, iminodibenzyl, which could reprogram the COX-2 catalyzed omega-6 PUFAs peroxidation in lung cancer by inhibiting delta-5-desaturase (D5D) activity. Iminodibenzyl breaks the conversion from dihomo-γ-linolenic acid (DGLA) to arachidonic acid, resulting in the formation of a distinct byproduct, 8-hydroxyoctanoic acid, in lung can

SUBMITTER: Pang L 

PROVIDER: S-EPMC8355066 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature