Inhibitory and ameliorative effect of heliomycin derived from actinomycete on induced hepatocellular carcinoma in rats.

The hepatoprotective activity of heliomycin obtained from the culture broth of actinomycete AB5 against diethylnitrosamine (DEN)-induced hepatic cancer in Wistar rats was estimated. Heliomycin exhibited a significant decrease in the levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) compared to the positive control. For instance, the heliomycin group after 20 weeks showed a significant decline in ALT, AST, and ALP values (70.75 ± 5.12, 140.25 ± 11.75, and 163.25 ± 18.66, respectively) compared to the positive control group (170.00 ± 9.55, 252.75 ± 12.33, and 278.00 ± 21.32, respectively). Additionally, the isolated compound showed a highly significant decrease in serum alpha-fetoprotein (AFP) levels. After 8, 16, and 20 weeks, the mean values of AFP in the heliomycin group revealed a highly significant decrease (33.62 ± 2.46, 30.00 ± 4.05, and 28.50 ± 2.64, respectively) compared to the positive control group (49.45 ± 3.03, 81.90 ± 6.70, and 90.75 ± 5.12, respectively). The histopathological investigation of liver sections supported the results of biochemical analysis. It was demonstrated that heliomycin showed histological improvement of hepatocytes and marked increase of nuclear pyknotic with clear cytoplasm, which is a sign of improving the apoptotic pathway of malignant cells. It also displayed marked fibrosis at most of the malignant cells and the development of some regenerative nodules. Heliomycin showed moderate immunoreactivity with alpha-fetoprotein (AFP), and proliferation cell nuclear antigen (PCNA) compared to the positive control group. To the best of our knowledge, this is the first study to report the anticancer activity of heliomycin against hepatocellular carcinoma in vivo.