title: 2-methoxyjuglone induces apoptosis in HepG2 human hepatocellular carcinoma cells and exhibits in vivo antitumor activity in a H22 mouse hepatocellular carcinoma model.
abstract: In order to discover anticancer agents from natural sources, an ethanol-soluble extract of the root bark of Juglans cathayensis was investigated and showed cytotoxic effects against various human cancer cell lines. A subsequent phytochemical study on the EtOAc-soluble fraction determined 2-methoxyjuglone (1) as one of the main active constituents. Compound 1 was shown to be cytotoxic against HepG2 cells. Morphological features of apoptosis were observed in 1-treated HepG2 cells, including cell shrinkage, membrane blebbing, nuclear condensation, and apoptotic body formation. Cell cycle analysis with propidium iodide staining showed that 1 induced cell cycle arrest at the S phase in HepG2 cells. Flow cytometric analysis with annexin V and propidium iodide staining demonstrated that 1 induced HepG2 cell apoptotic events in a dose-dependent manner (0-8 μg/mL). Western blot analysis of apoptosis-related proteins revealed that 1 induces HepG2 cell apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway (intrinsic pathway). An in vivo experiment using tumor-bearing mice showed that treatment with 1 at 0.5 and 1.0 mg/kg per day decreased the tumor mass by 56% and 67%, respectively.
authors.affiliation: Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Faculty of Pharmacy, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Heng-Yi
authors.initials: HY
authors.lastname: Yu
authors.forename: Xiao-Qiong
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Xue-
authors.initials: X
authors.lastname: Li
authors.forename: Fan-Bo
authors.initials: FB
authors.lastname: Zeng
authors.forename: Han-Li
authors.initials: HL
authors.lastname: Ruan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D031324:Juglans / Q000737:chemistry*; D051379:Mice; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects
chemical_list: C582936:2-methoxyjuglone; D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones