Efficacy of Berberine on PGE2 Levels in Malignant Melanoma

Berberine is a plant alkaloid that first appeared in the literature in 1933 as an antimicrobial agent in the treatment of trachoma. Since then, the potential of berberine, a selective COX-2 inhibitor reported to have limited side effects, has grown. Cyclooxygenase-2 (COX-2) is an enzyme necessary in the production of prostaglandins, especially Prostaglandin E2 (PGE2) which is vital in the activation of pathways that mediate proliferation, angiogenesis, and chemotherapeutic resistance in certain types of cancer. In fact, recent studies have shown that PGE2 is of significance in malignant melanoma, which kills 65,000 people a year worldwide. The goal of this project was to test the effect of berberine on A375 malignant melanoma cells with concentrations of 0.5 millimole (mM), 1.0 mM, 1.5 mM, 2.0 mM, 2.5 mM, and 3.0 mM. In particular PGE2 production was evaluated, which, in previous research, has been shown to be directly related to COX-2 activity. Results from ELISA demonstrated that a decrease in cell viability directly correlated to the decrease in the production of PGE2 (p<0.01) for concentrations greater than 1.0 mM. Additionally, a migration assay determined that berberine significantly decreased the migratory response toward media (p<0.01). Further research includes investigating the efficacy of celecoxib, a COX-2 selective nonsteroidal anti-inflammatory drug (NSAID) which shows promise as an anti-cancer agent, on PGE2. However, celecoxib displays undesirable side effects, such as increased risk of stroke, heart attack, and ulcer. Findings of decreased levels of PGE2 with berberine may have major implications on reducing the amount of celecoxib and increasing the use of berberine in the drug therapy of malignant melanoma.