title: Juglanthraquinone C, a novel natural compound derived from Juglans mandshurica Maxim, induces S phase arrest and apoptosis in HepG2 cells.
abstract: Juglanthraquinone C (1,5-dihydroxy-9,10-anthraquinone-3-carboxylic acid, JC), a naturally occurring anthraquinone isolated from the stem bark of Juglans mandshurica, shows strong cytotoxicity in various human cancer cells in vitro. Here, we first performed a structure-activity relationship study of six anthraquinone compounds (JC, rhein, emodin, aloe-emodin, physcion and chrysophanol) to exploit the relationship between their structural features and activity. The results showed that JC exhibited the strongest cytotoxicity of all compounds evaluated. Next, we used JC to treat several human cancer cell lines and found that JC showed an inhibitory effect on cell viability in dose-dependent (2.5-10 μg/ml JC) and time-dependent (24-48 h) manners. Importantly, the inhibitory effect of JC on HepG2 (human hepatocellular carcinoma) cells was more significant as shown by an IC(50) value of 9 ± 1.4 μg/ml, and 36 ± 1.2 μg/ml in L02 (human normal liver) cells. Further study suggested that JC-induced inhibition HepG2 cell proliferation was associated with S phase arrest, decreased protein expression of proliferation marker Ki67, cyclin A and cyclin-dependent kinase (CDK) 2, and increased expression of cyclin E and CDK inhibitory protein Cip1/p21. In addition, JC significantly triggered apoptosis in HepG2 cells, which was characterized by increased chromatin condensation and DNA fragmentation, activation of caspase-9 and -3, and induction of a higher Bax/Bcl2 ratio. Collectively, our study demonstrated that JC can efficiently inhibit proliferation and induce apoptosis in HepG2 cells.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yao
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Zhang
authors.forename: Lu-Guo
authors.initials: LG
authors.lastname: Sun
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Bao
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zheng
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Yu
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.forename: Guan-Nan
authors.initials: GN
authors.lastname: Wang
authors.forename: Yu-Xin
authors.initials: YX
authors.lastname: Li
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation; D056945:Hep G2 Cells; D006801:Humans; D031324:Juglans / Q000737:chemistry*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D013329:Structure-Activity Relationship; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D018797:Cell Cycle Proteins; D004365:Drugs, Chinese Herbal; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C575655:juglanthraquinone C; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9