title: 13-methyltetradecanoic acid exhibits anti-tumor activity on T-cell lymphomas in vitro and in vivo by down-regulating p-AKT and activating caspase-3.
abstract: 13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, induces apoptosis in human cancer cells. We investigated the inhibitory effects and mechanism of action of 13-MTD on T-cell non-Hodgkin's lymphoma (T-NHL) cell lines both in vitro and in vivo. Growth inhibition in response to 13-MTD was evaluated by the cell counting kit-8 (CCK-8) assay in three T-NHL cell lines (Jurkat, Hut78, EL4 cells). Flow cytometry analyses were used to monitor the cell cycle and apoptosis. Proteins involved in 13-MTD-induced apoptosis were examined in Jurkat cells by western blotting. We found that 13-MTD inhibited proliferation and induced the apoptosis of T-NHL cell lines. 13-MTD treatment also induced a concentration-dependent arrest of Jurkat cells in the G1-phase. During 13-MTD-induced apoptosis in Jurkat cells, the cleavage of caspase-3 and poly ADP-ribose polymerase (PARP, a caspase enzymolysis product) were detected after incubation for 2 h, and increased after extending the incubation time. However, there was no change in the expression of Bcl-2 or c-myc proteins. The appearance of apoptotic Jurkat cells was accompanied by the inhibition of AKT and nuclear factor-kappa B (NF-κB) phosphorylation. In addition, 13-MTD could also effectively inhibit the growth of T-NHL tumors in vivo in a xenograft model. The tumor inhibition rate in the experimental group was 40%. These data indicate that 13-MTD inhibits proliferation and induces apoptosis through the down-regulation of AKT phosphorylation followed by caspase activation, which may provide a new approach for treating T-cell lymphomas.
authors.affiliation: Department of Medical Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, P. R. China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Cai
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Huang
authors.forename: Dong
authors.initials: D
authors.lastname: Qian
authors.forename: Kailin
authors.initials: K
authors.lastname: Chen
authors.forename: Junhua
authors.initials: J
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Tian
authors.forename: Tianxin
authors.initials: T
authors.lastname: Lin
authors.forename: Tongyu
authors.initials: T
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009227:Myristic Acids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D009227:Myristic Acids; D016328:NF-kappa B; D009363:Neoplasm Proteins; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; C027331:13-methyltetradecanoic acid