Oral glutamine (AES‐14) supplementation inhibits PI‐3k/Akt signaling in experimental breast cancer

Abstract

GLN supplementation inhibited the PI-3K/Akt pathway that is thought to be important in increasing cell survival during tumorigenesis. These results are in agreement with our hypothesis that GLN counteracts the effects of DMBA and blocks carcinogenesis in vivo.

Modulation of p53 and c-myc in DMBA-Induced Mammary Tumors by Oral Glutamine

“…3, p85 PI3K-e; 805 ± 88 vs. 2,503 ± 193; P < 0.05). These results are consistent with our previously published data of inhibition of anti-apoptotic Akt signaling in mammary tissue of rats with experimental breast cancer (31).…”

“…The results published elsewhere (22,31,34), showed that tumor development was significantly (P = 0.007, GLN vs. control, Fisher Exact Test) reduced by GLN supplementation at the end of the study (11 wk after DMBA application). The GLN-supplemented group had 50% less tumors in comparison with the control group (Fig.…”

“…Following blocking with 5% non-fat milk in TBS-T buffer (100mM Tris, pH 7.5; 150mM NaCl; 0.1% Tween 20) for 1 h at room temperature, the membranes were incubated overnight at 4°C in primary antibody and 1 h at room temperature with HRP-labeled secondary antibodies (Santa Cruz Biotech Inc., Santa Cruz, CA). The following primary antibodies were used as recommended by the manufacturers: anti-phospho p53, anti-p21Waf1/Cip1, anti-PTEN, anti-phospho mdm2, anti-(p85) PI3K, anti-phospho-c-myc, and anti-c-myc (Cell Signaling Technology, Beverly, MA protein levels of IGF-IR was reported previously (31). The equal protein loading was verified by re-probing the membranes with anti-β actin antibody.…”

“…Our previous studies showed reduction in circuVol. 54 18s> Target gene> lating-and breast tissue levels of IGF-I by GLN supplement in rats with DMBA-induced breast cancer (21,31). The decreased protein levels of IGF-I, together with a reduction in IGF-IR protein were associated with down-regulation of Akt and Bcl-2, and up-regulation of Bad, Bax, and caspase-3.…”

Stressing Out Over Survival: Glutamine as an Apoptotic Modulator

“…They found that a GLN enriched diet reduced tumor GSH-to-oxidized glutathione (GSSG) ratios, up-regulated Bax and caspase-3 expression and reduced Bcl-2 levels, essentially reducing the "apoptotic threshold" of the tumor. This same group also reported that GLN-enriched diets depressed insulin-like growth factor-1 (IGF1), its receptor (IGF1R) and PKB/Akt protein levels and enhanced Bad expression in breast tumors more than in normal tissues, again depressing survival signaling in cancerous tissue [138]. The mechanism by which GSH levels and anti-apoptotic signaling are selectively repressed by GLN-enriched diets in chemically induced fibrosarcoma and breast tumors is unclear, but the implication from this research thus far is that the reluctance to use GLN-enriched nutritional regimens in cancer patients may be unfounded.…”