title: Effect of ximenynic acid on cell cycle arrest and apoptosis and COX-1 in HepG2 cells.
abstract: Ximenynic acid is a conjugated enyne fatty acid, which is currently of interest due to its anti-inflammatory activity. Due to the association between inflammation and cancer, the present study was designed to investigate the anti‑cancer activity of ximenynic acid in the HepG2 human hepatoma cell line and the underlying mechanisms. The current study demonstrated the anti‑proliferation and pro‑apoptosis activities of ximenynic acid by cell viability assay and flow cytometry analysis. The expression of anti‑apoptosis protein silent information regulator T1 (SIRT1) was significantly suppressed by ximenynic acid. Furthermore, ximenynic acid blocked G1/S phase transition by inhibiting the protein expression of the cell cycle‑associated protein general control of amino acid synthesis yeast homolog like 2 (GCN5L2), and the mRNA expression of cyclin D3 and cyclin E1. Furthermore, ximenynic acid suppressed the expression of angiogenesis‑associated genes, including vascular endothelial growth factor (VEGF)‑B and VEGF‑C. Finally, ximenynic acid significantly inhibited the expression of cyclooxygenase‑1 (COX‑1) mRNA and protein, however COX‑2 expression was not reduced. The results of the present study suggested that ximenynic acid may inhibit growth of HepG2 cells by selective inhibition of COX‑1 expression, which leads to cell cycle arrest, and alters the apoptosis pathway and expression of angiogenic factors. The current study aimed to investigate whether ximenynic acid might be developed as novel anticancer agent.
authors.affiliation: Department of Food Science and Nutrition, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Cai
authors.affiliation: Institute of Developmental and Regenerative Biology, Hangzhou Normal University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth 02042G, Australia.
authors.forename: Yandi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Developmental and Regenerative Biology, Hangzhou Normal University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Zunyi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth 02042G, Australia.
authors.forename: D S
authors.initials: DS
authors.lastname: Hettiarachchi
authors.affiliation: Department of Food Science and Nutrition, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.
authors.forename: Duo
authors.initials: D
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D009829:Oleic Acids / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009829:Oleic Acids; D051545:Cyclooxygenase 1; D053148:Caspase 3; C053760:ximenynic acid