Berberine induces apoptosis by suppressing the arachidonic acid metabolic pathway in hepatocellular carcinoma

Berberine (BBR) has been suggested as a potential candidate anticancer agent due to its high anticancer activity and multiple mechanisms. In the present study, the inhibitory effect of BBR on hepatocellular carcinoma (HCC) via the suppression of the arachidonic acid (AA) metabolic pathway was investigated. BBR was demonstrated to reduce the viabilities of H22, HepG2 and Bel-7404 cells, in a dose-and time-dependent manner, and increase the number of apoptotic cells. BBR induced the translocation of apoptosis-inducing factor between the mitochondria and the nucleus, and had no effects on the protein expression levels of caspase-3 or -9. In addition, BBR significantly suppressed the protein expression levels of cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)-2 and elevated the content ratio of AA to prostaglandin E2 (PGE2). Furthermore, BBR reduced the volume and weight of tumors in a H22 transplanted tumor model in mice. The results of the present study demonstrated that elevation in the ratio of AA to PGE2 via suppression of the protein expression of cPLA2 and COX-2 in the AA metabolic pathway is involved in the inhibitory effect of BBR in HCC.