title: Ampelopsin induces apoptosis in HepG2 human hepatoma cell line through extrinsic and intrinsic pathways: Involvement of P38 and ERK.
abstract: Our results showed that ampelopsin significantly inhibited cell viability of hepatoma HepG2 cells using MTT assay. We further investigated the mechanism of anticancer activity by ampelopsin, it showed that ampelopsin induced apoptosis of HepG2 cells using DAPI assay and flow cytometry, which was confirmed by activation of PARP. Next, activation of the caspase cascades were demonstrated, including caspase-8, -9 and -3. We also found that ampelopsin increased the levels of death receptor 4 (DR4), death receptor 5 (DR5) and decreased the expression of Bcl-2 protein, which led to an increase of the Bax/Bcl-2 ratio. Meanwhile, the release of cytochrome c from mitochondria was observed. Ampelopsin decreased the levels of iNOS and COX-2 but had no impact on the level of reactive oxygen species (ROS). In addition, ampelopsin activated ERK1/2 and P38, but little JNK1/2 activation was detected. Further investigation showed that suppression of P38 activation by SB203580 increased the cell viability and also prevented cleavage of caspase-3 and PARP, inhibition of ERK1/2 with U0126 had the opposite action. In conclusion, our results indicated that ampelopsin mainly elicited apoptosis through extrinsic and intrinsic pathway and that ERK1/2 and P38 had opponent effects on the apoptosis.
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu 241002, China. Electronic address: juliaqi@163.com.
authors.forename: Shimei
authors.initials: S
authors.lastname: Qi
authors.affiliation: Health Science of College, Wuhan Institute of Physical Education, Wuhan 430000, China.
authors.forename: Xianjuan
authors.initials: X
authors.lastname: Kou
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu 241002, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu 241002, China.
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Department of Biochemistry, Wannan Medical College, Wuhu 241002, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; C106407:ampelopsin; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Ampelopsin; Apoptosis; Bcl-2; Death receptor; ERK; P38