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.

Human fetal intestinal epithelial cells metabolize and incorporate branched chain fatty acids in a structure specific manner

“…via Akt) and induces ER stress and/or an apoptotic response [15–17]. In particular, incubation of cells with BCFA also causes apoptosis [18, 19]. In these studies, non-esterified BCFA were solubilized by non-ionic surfactants (Tween 80) and therefore were present as unbound fatty acids.…”

“…The high level of BCFA incorporation in our experiments, and apparently low toxicity in vitro suggests these cells are indeed highly tolerant and may well have evolved specific uses for BCFA at uniquely in vivo high exposures in the late term fetal gut. In contrast, iso -15:0 induces apoptosis in various human cancer cells with IC 50 ranging from 0.04 mM to 0.16 mM, including breast cancer (MCF-7), T-cell lymphomas (Jurkat and Hut78 cells), prostate cancer (E4 and DU145 cells), and hepatocarcinoma (NCI-H1688 cells)[18, 19]. In these studies, iso -15:0 was not solubilized by albumin, raising the possibility that the free fatty acid concentration was relatively high.…”

Does the Fat Tailed Damara Ovine Breed Have a Distinct Lipid Metabolism Leading to a High Concentration of Branched Chain Fatty Acids in Tissues?

“…Indeed, it was reported that iso and anteiso BCFA show antitumoral activity in human cancer cells [19], [20] and also reduce the incidence of necrotizing enterocolitis, a devastating intestinal disease affecting premature infants [21]. However, as far as we know, there is no information available about the potential health effects of the non-terminal mono- and di-methyl BCFA.…”

Pterostilbene Induces Cell Apoptosis and Cell Cycle Arrest in T-Cell Leukemia/Lymphoma by Suppressing the ERK1/2 Pathway

“…The incidence of T-cell leukemia/lymphoma accounts for 30% of all non-Hodgkin lymphomas in Asia [2]. T-cell leukemia/lymphoma has a poor prognosis and is more aggressive than B-cell lymphoma.…”