Dietary glycine prevents the development of liver tumors caused by the peroxisome proliferator WY-14,643

Abstract

Previous studies demonstrated that dietary glycine prevents elevated rates of cell proliferation following treatment with the peroxisome proliferator and liver carcinogen WY-14,643. Since increased cell replication is associated with the development of hepatic cancer caused by peroxisome proliferators, glycine may have anti-cancer properties. Therefore, experiments were designed to test the hypothesis that dietary glycine would inhibit the hepatocarcinogenic effect of WY-14,643. Male F344 rats were fed four different NIH 07-based diets: 5% glycine; 5% valine for nitrogen balance (control); 0.1% WY-14,643 + 5% valine (WY-14,643); 0.1% WY-14,643 + 5% glycine (WY-14,643 + glycine). Food consumption did not differ among the groups, but WY-14,643-fed rats weighed 10-25% less than expected based on previous studies. Serum glycine levels were elevated 4-5-fold by glycine-containing diets; however, the 10-fold increase in peroxisomal enzyme activity caused by WY-14,643 was unaffected by the addition of 5% glycine to the diet. After 22 weeks, livers from rats fed WY-14,643 had a similar incidence and multiplicity of proliferative lesions (foci and adenomas) to those fed WY-14,643 + glycine. Moreover, cell proliferation in the surrounding 'normal' parenchyma (labeling index approximately 4%) and foci (labeling index approximately 50%) did not differ between WY-14,643 and WY-14,643 + glycine-fed rats. However, after 51 weeks of dietary exposure to WY-14,643, glycine prevented formation of small (0-5 mm diameter) tumors by 23% and inhibited the development of medium size (5-10 mm) tumors by 64%. Furthermore, glycine prevented the formation of the largest tumors (>10 mm) by nearly 80%. Thus, glycine did not inhibit early foci formation; however, it significantly decreased their ability to progress to tumors. Moreover, the inhibitory effect of glycine was greater with increasing tumor size. These studies demonstrate that dietary glycine prevents the development of hepatic tumors caused by the peroxisome proliferator WY-14,643 consistent with the idea that it may be an effective chemopreventive agent.

The effect of dietary glycine on the hepatic tumor promoting activity of polychlorinated biphenyls (PCBs) in rats

“…But the data overall indicate that Kupffer cells likely do not contribute to the tumor promoting activities of PCB-77 and PCB-153. These results clearly differ from those of Rose et al (1999a), who found that Kupffer cell inactivation by dietary glycine inhibited liver carcinogenesis by the peroxisome proliferator Wy-14,643. The findings of the present study imply that Kupffer cell activation may not be essential for hepatic tumor promotion.…”

“…For this, we examined the ability of dietary glycine to inhibit PCB-induced tumor promotion, since several studies have shown that glycine decreases the production of superoxide and TNF-α by Kupffer cells (Ikejima et al 1996;Rose et al 1999a;Rose et al 1997a;Rusyn et al 1999). The inhibition by glycine of TNF-α production by Kupffer cells is not as strong as using agents such as gadolinium chloride or methyl palmitate, but that may be an advantage for a therapeutic agent (Rentsch et al 2005).…”

“…This dose was chosen based on previous studies (Berberian et al 1995;Glauert et al 2005;Stemm et al 2005;Tharappel et al 2002) Glycine or casein (casein contains 1.8% glycine) was fed in the unrefined diet at 5% starting on the 14th day after DEN initiation until the end of the experiment. Glycine was fed at the 5% level because of previous studies showing that this level inhibited the induction of cell proliferation and hepatic tumors by peroxisome proliferators (Rose et al 1999a;Rose et al 1997a). The diet was administered ad libitum in glass feeding cups.…”

Dietary Glycine Inhibits Angiogenesis During Wound Healing and Tumor Growth

“…13,14 Previous studies have shown that dietary glycine inhibits the growth of B16 melanoma tumors in mice 15 and certain carcinogen induced liver tumors. 16 In these studies glycine inhibited growth of an established tumor in vivo but did not have any cytotoxic effect on tumor cells in vitro. Thus, Rose postulated that glycine's primary effect would be on host tissue but convincing evidence for this hypothesis was not provided.…”

Glyphosate, pathways to modern diseases IV: cancer and related pathologies

“…In direct contradiction, however, glycine has been shown to prevent tumorigenesis [122] and it is a potent anti-angiogenic nutrient that suppresses tumour growth, possibly through activation of a glycine-gated chloride channel [123]. Impaired glycine synthesis likely has other adverse effects as well, such as the possibility that glyphosate interferes with glycine conjugation of benzenebased compounds.…”