Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet

Abstract

The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein source on hepatic tumor promotion in a mouse model reflecting aspects of non-alcoholic fatty liver disease (NAFLD). A high-fat liquid diet with casein as the protein source promotes hepatic injury and tumor promotion in diethylnitrosamine-treated mice. Replacing casein with a soy protein isolate led to a pronounced diminishment of tumor promotion and associated hepatic injury and inflammation. The study thus demonstrates that a dietary protein source can have beneficial, preventative effects on hepatic tumor promotion. AbstractAlcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/b-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/b-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets.

Genistein Improves Liver Damage in Male Mice Exposed to Morphine

“…Morphine can cause injuries to liver and renal tissues. [ 5 12 ] Oxidative stress is a factor greatly involved in the liver damage caused by drugs and toxins. The increased activity of liver enzymes in serum indicates hepatic damage, which leads to the reduced performance of liver cells.…”

“…[ 4 ] Nowadays, according to the epidemiologic studies on the role of soybean in preventing some cancers as well as its effects on preventing cardiovascular diseases and diabetes, consumption of soy-containing food has found a special place in the diet of people. [ 5 ] Genistein, with molecular formula 4', 5, 7-trihydroxy-isoflavone, is the major isoflavone in soybean. [ 6 ] It is the isoflavone that has received the most attention due to its estrogenic, neuroprotective, antioxidant, anti-inflammatory, and anti-proliferative effects.…”

Effects of Resistance Exercise and Fermented Soybean Consumption on Glucose Tolerance and Expressions of Immune Senescence-Related Myokines in Middle-Aged Obese Rats

“…Han et al31 reported that soy leaf extracts are effective at reducing proinflammatory cytokines levels in blood vessels, including TNF-α, IL-6, IL-1β, CCL2, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1. Moreover, Mercer et al32 reported that soy protein isolates have inhibitory effects on high-fat diet-induced hepatoma proliferation in mice, by reducing IL-6 and TNF-α expression. Consistent with these previous studies, our results indicate that consumption of fermented soybeans is effective at preventing inflammation and increasing immune system function during senescence and obesity.…”

A Comprehensive Review Evaluating the Impact of Protein Source (Vegetarian vs. Meat Based) in Hepatic Encephalopathy

“…In addition, soy supplementation restored the activity of antioxidant enzymes (glutathione peroxidase and superoxide dismutase), reduced lipid peroxidation and improved histological features of the liver injury [ 44 ]. Additionally, other studies have reported beneficial effects of soy proteins in improving hepatic steatosis and hepatocellular carcinoma (HCC) [ 45 , 46 ]. Specifically, soy protein supplementation significantly reduced hepatocyte fat accumulation and tumor growth in high fat diet (HFD)- diethyl nitrosamine (DEN) and ethanol fed mice.…”