Knockdown of delta-5-desaturase promotes the anti-cancer activity of dihomo-γ-linolenic acid and enhances the efficacy of chemotherapy in colon cancer cells expressing COX-2.

摘要: Cyclooxygenase (COX), commonly overexpressed in cancer cells, is a major lipid peroxidizing enzyme that metabolizes polyunsaturated fatty acids (ω-3s and ω-6s). The COX-catalyzed free radical peroxidation of arachidonic acid (ω-6) can produce deleterious metabolites (e.g. 2-series prostaglandins) are implicated development. Thus, COX inhibition has been intensively investigated as complementary therapeutic strategy for cancer. However, our previous study demonstrated radical-derived byproduct (8-hydroxyoctanoic acid) formed from dihomo-γ-linolenic (DGLA, the precursor inhibit colon cell growth. We thus hypothesize (~90% patients) be taken advantage to suppress growth by knocking down delta-5-desaturase (D5D, key converts DGLA acid). In addition, D5D knockdown along with supplement may enhance efficacy chemotherapeutic drugs. After HCA-7 colony 29 cells HT-29 (human lines high low levels, respectively), antitumor activity was significantly enhanced formation threshold range (~0.5-1.0μM) 8-hydroxyoctanoic acid. contrast, treatment did not when knocked only limited amount formed. also cytotoxicities various drugs, including 5-fluorouracil, regorafenib, irinotecan, potentially through activation pro-apoptotic proteins, e.g. p53 caspase 9. For first time, we have utilized suppressing This finding provide new option besides optimize therapy. outcome this translational research will guide us develop novel ω-6-based diet-care combination current chemotherapy prevention treatment.