Spirulina was shown to exert anti-inflammatory, antioxidant, hepatoprotective properties, and
anticancer activity. This study was done to investigate the protective effects of spirullina on DEN
induced hepatocarcinogensis in rats. Fourty-five male albino rats were divided into three groups.
Group Ӏ :(normal control group): rats administered distilled water only. Group II: rats received
diethylnitrosoamine (200 mg/kg b.wt/i.p), 2 weeks later rats received (2 ml/kg b.wt) Carbon
tetrachloride (CCl4) orally at 1:1 dilution in corn oil as a promoter of carcinogenic effect. DEN and
CCl4 injections were repeated once again after 1 month from first DEN injection. Group III: rats
received DEN then treated with spirullina platensis at a dose level of (800 mg/kg b.wt/orally)
dissolved in distilled water for 6 weeks. DEN induced HCC showed significant increase in hepatic
marker enzymes (ALT and ALP), total bilirubin and alpha fetoprotein (AFP) with marked decrease
in serum albumin concentration. Also, the results of molecular analysis in liver tissue revealed
significant up-regulation in TNF-α gene expression level. Conversely, down-regulation in tumor
suppressor gene p53 and Cyp2E1 gene expression compared with control group. Treatment with
spirullina platensis to DEN induced HCC protects the liver cells from damage by regulating the
biochemical parameters. Spirullina platensis was able to mitigate liver tissue damage induced by
DEN through increasing of Cyp2E1 and P53 in addition to decreasing TNF-α gene expression level
and ameliorate all serum liver function parameters. The obtained results suggest spirullina platensis
can inhibit the proliferation of HCC cells through inducing tumor cell apoptosis via activation of the
p53 pathway, improvement of detoxification Enzyme and suppression of inflammation by
inhibition of TNF-α overexpression. Spirullina may thus be used as a potentially promising agent to
inhibit HCC cell proliferation and may be a novel natural product for the management of HCC.