Hepatocellular carcinomas are promoted by tocopheryl acetate but eliminated by tocopheryl succinate

Background

The major causes of hepatocellular carcinomas are Aflatoxin, hepatitis B and hepatitis C viruses.

Alpha tocopherol and its acetate and succinate esters have each been reported as counteracting cancer development in humans and rodents. We have investigated their salutary effect in both poor and high quality diets in rainbow trout Oncorhynchus mykiss as a model.

Methods

Hepatocellular carcinomas (HCCs) were induced in rainbow trout by dietary aflatoxin B1 (AfB1). A matrix of different levels of several vitamins and vitamin analogues were included in selected diets as possible anticancer agents. Identification of HCCs was made by histopathology.

Results

1.) Elevated dietary tocopheryl acetate (E-Ac) caused a marked increase in liver size and in AfB1-induced HCCs in rainbow trout. 2.) Poor diets increased the HCC incidence. 3.) Elevated dietary tocopheryl succinate (E-Su) nearly eliminated HCC development in fish fed complete diets. Tocopheryl succinate in poor diets reduced HCCs by 77% compared to tocopheryl acetate diets. 4.) Trans-retinoic acid also reduced HCC incidence. 5.) Vitamins A and D deficiency caused tumor increases but had no effect on liver size. 6.) The use of casein and dextrin in the place of soybean textured vegetable protein, in poor diets nearly eliminated the HCC risk. 7.) Trout sera showed all three vitamin forms; free α-tocopherol (E-OH), tocopheryl acetate (E-Ac) and tocopheryl succinate (E-Su), from diets containing any of these vitamin analogues, suggesting both de-esterification and trans-esterification. 8.) E-Su is discussed in the light of an anti-cancer agent that is non toxic to normal tissue but that cohorts to it are needed.

Conclusions

Increased dietary E-Ac escalated AfB1 induced HCCs and caused hepatomegaly in rainbow trout, while E-Su eliminated the HCC risk as shown by histopathology.