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.
Highlights
T-cell lymphomas are a heterogeneous group of non-Hodgkin’s lymphomas (NHLs), whose incidence accounts for 30% of nonHodgkin’s lymphomas in Asia
Saturated and unsaturated fatty acids have been reported to have antineoplastic effects [4,5,6,7]. 13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, can inhibit the growth of various cancer cell lines in vitro or in vivo by inducing apoptosis without significant toxic side effects [8,9,10]
We speculated that 13-MTD might induce apoptosis in Tcell non-Hodgkin’s lymphoma (T-NHL) cells by down-regulating p-AKT, which is important for NHL cell survival
Summary
T-cell lymphomas are a heterogeneous group of non-Hodgkin’s lymphomas (NHLs), whose incidence accounts for 30% of nonHodgkin’s lymphomas in Asia. 13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, can inhibit the growth of various cancer cell lines (e.g. breast cancer cells, prostate cancer cells, hepatocellular carcinoma cells, leukemia cells, human bladder cancer cells) in vitro or in vivo (human hepatocellular carcinoma LCI-D35 and human prostate cancer DU 145 cell lines) by inducing apoptosis without significant toxic side effects [8,9,10]. We speculated that 13-MTD might induce apoptosis in T-NHL cells by down-regulating p-AKT, which is important for NHL cell survival. We investigated the anti-tumor effect of 13-MTD on T-NHL cell lines in vitro and in vivo, and examined the involvement of AKT and its downstream signaling pathway to elucidate the possible cytostatic mechanism of 13-MTD on T-NHL cells
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