title: Natural borneol, a monoterpenoid compound, potentiates selenocystine-induced apoptosis in human hepatocellular carcinoma cells by enhancement of cellular uptake and activation of ROS-mediated DNA damage.
abstract: Selenocystine (SeC) has been identified as a novel compound with broad-spectrum anticancer activities. Natural borneol (NB) is a monoterpenoid compound that has been used as a promoter of drug absorption. In the present study, we demonstrated that NB significantly enhanced the cellular uptake of SeC and potentiated its antiproliferative activity on HepG2 cells by induction of apoptosis. NB effectively synergized with SeC to reduce cancer cell growth through the triggering apoptotic cell death. Further mechanistic studies by Western blotting showed that treatment of the cells with NB and SeC activated the intrinsic apoptotic pathway by regulation of pro-survival and pro-apoptotic Bcl-2 family proteins. Treatment of the cells with NB and SeC induced the activation of p38MAPK and inactivation of Akt and ERK. NB also potentiated SeC to trigger intracellular ROS generation and DNA strand breaks as examined by Comet assay. Moreover, the thiol-reducing antioxidants effectively blocked the occurrence of cell apoptosis, which confirmed the important role of ROS in cell apoptosis. Taken together, these results reveal that NB strongly potentiates SeC-induced apoptosis in cancer cells by enhancement of cellular uptake and activation of ROS-mediated DNA damage. NB could be further developed as a chemosensitizer of SeC in treatment of human cancers.
authors.affiliation: College of Light Industry and Food Sciences, South China University of Technology, Guangzhou, China. jysu@scut.edu.cn
authors.forename: Jianyu
authors.initials: J
authors.lastname: Su
authors.forename: Haoqiang
authors.initials: H
authors.lastname: Lai
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.forename: Yum-Shing
authors.initials: YS
authors.lastname: Wong
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D001892:Camphanes / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004789:Enzyme Activation; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000187:drug effects; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017279:Selenocysteine / Q000378:metabolism / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001892:Camphanes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D017279:Selenocysteine; D020169:Caspases; C022871:isoborneol