title: Ethyl acetate extract of Hypericum japonicum induces apoptosis via the mitochondria-dependent pathway in vivo and in vitro.
abstract: The widely-used Chinese medicinal herb Hypericum japonicum, also known as Hypericum japonicum Thunb or Tianjihuang, displays potent anti‑carcinogenic effects against liver cancer. However, the molecular mechanism underlying the therapeutic effects of Hypericum japonicum remains to be elucidated. The present study investigated the in vivo efficacy of ethyl acetate extract of Hypericum japonicum (EAEHJ) against tumor growth in an H22 cell‑bearing liver cancer mouse model. Treatment with EAEHJ significantly reduced tumor weight, but had no effect on murine body weight. The results of the present study also showed that EAEHJ induced H22 cell apoptosis in vivo. In addition, the anti‑carcinogenic effects of EAEHJ were investigated in vitro. The results of the present study demonstrate that both phospholipid asymmetry in the plasma membrane and mitochondrial membrane potential were deregulated in HepG2 human hepatoma cells, following treatment with EAEHJ. Treatment with EAEHJ also increased the ratio of pro‑apoptotic B‑cell lymphoma 2 (Bcl‑2)‑associated X protein (Bax) to anti‑apoptotic Bcl‑2, and activated the caspase‑9 signaling pathway. These results suggest that EAEHJ is able to trigger the apoptosis of liver cancer cells via the mitochondria-dependent pathway.
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Qunchuan
authors.initials: Q
authors.lastname: Zhuang
authors.affiliation: Department of Medical Technology, Fujian Health College, Fuzhou, Fujian 350101, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Youqin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jiumao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, P.R. China.
authors.forename: Faze
authors.initials: F
authors.lastname: Lai
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Xuzheng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, P.R. China.
authors.forename: Xindeng
authors.initials: X
authors.lastname: Lin
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D000085:Acetates; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000085:Acetates; D016588:Anticarcinogenic Agents; C494826:BAX protein, human; C494827:Bax protein, mouse; D010936:Plant Extracts; D051028:bcl-2-Associated X Protein; C007650:ethyl acetate; C505407:CASP3 protein, human; C506433:CASP9 protein, human; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053148:Caspase 3; D053453:Caspase 9