title: 12-Deoxyphorbol 13-palmitate mediated cell growth inhibition, G2-M cell cycle arrest and apoptosis in BGC823 cells.
abstract: The highly toxic monomer 12-deoxyphorbol 13-palmitate (G) was extracted from the roots of Euphorbia fischeriana. Our experimental data confirmed studies showing that 12-deoxyphorbol 13-palmitate had certain antitumor activities. The MTT method, soft agar experiments, and nude mouse tumor experiments proved that 12-deoxyphorbol 13-palmitate inhibited the growth of BGC823 cells. We found that the drug could induce cell cycle arrest at the G2-M checkpoint in BGC823 cells. The compound also induced apoptosis as assayed by Annexin-V-FITC/PI dual labeling, AO/EB dyeing, and caspase-3 and caspase-9 activity. The reduction in expression of cyclin B1 protein and the increased activity of reactive oxygen species were observed in BGC823 cells treated with 12-deoxyphorbol 13-palmitate for 24 h. In addition, we found down-regulation of cdc2/cyclin B, cyclin A and p-chk1 in tumor cells. There was also up-regulation of Bax, p53, p21, and IκB-α and down-regulation of Bcl-2 and NF-κB by WB. Our studies may define a novel mechanism by which 12-deoxyphorbol 13-palmitate inhibits tumor cell growth and induces apoptosis. The results of our current studies provided strong experimental evidence for the use of 12-deoxyphorbol 13-palmitate as a potential preventive and/or therapeutic agent in cancer.
authors.affiliation: Department of Immunology, Qiqihar Medical University, No. 333 BuKui Street, Qiqihar, Heilongjiang, 161006, PR China. xhymy2005@163.com
authors.forename: Hui-Yu
authors.initials: HY
authors.lastname: Xu
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Chen
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: You-Yong
authors.initials: YY
authors.lastname: Lv
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056744:Cyclin B1 / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D010168:Palmitates / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C582659:12-deoxyphorbol 13-palmitate; D000970:Antineoplastic Agents; D056744:Cyclin B1; D010168:Palmitates; D010703:Phorbol Esters; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053453:Caspase 9