title: Berberine induces apoptosis by suppressing the arachidonic acid metabolic pathway in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Pharmacology, Basic Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Basic Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ou
authors.initials: O
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Basic Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Mujie
authors.initials: M
authors.lastname: Kan
authors.affiliation: Department of Pharmacology, Basic Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Basic Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Shao
authors.affiliation: Department of Pharmacology, Basic Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, Basic Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, China‑Japan Union Hospital of Jilin University, Chanchun, Jilin 130031, P.R. China.
authors.forename: Xuewen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Basic Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Manitoba Institute of Cell Biology and Faculty of Pharmacy, University of Manitoba, Winnipeg, MB R3E 0V9, Canada.
authors.forename: Songyan
authors.initials: S
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D054467:Phospholipases A2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001599:Berberine; D016718:Arachidonic Acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D054467:Phospholipases A2; D015232:Dinoprostone