ABSTRACT
BACKGROUND: Most hepatocellular carcinoma cases are diagnosed at late stages of the disease, which makes it the second cause of cancer mortality worldwide. For advanced-stage patients, chemotherapeutic drugs are the best treatment option; however, their adverse effects and high cost are still major obstacles for effective treatment. Spirulina microalga is a rich source of nutritional and bioactive elements and potential pharmaceuticals, which has an -proliferative effect against several cancer cell lines. It also has a prophylactic effect against the early stages of some cancer models, including hepatocellular carcinoma. AIMS: The present study was carried out to evaluate the therapeutic anticarcinogenic effect of spirulina against advanced murine hepatocellular carcinoma. MAIN METHODS: Hepatocarcinoma was induced by a single injection of diethylnitrosamine (100 mg/kg, intraperitoneally) followed by 22 weekly injections of carbon-tetrachloride (0.5 mg/kg, i.p). Spirulina (250 and 500 mg/kg bw) was given orally, from week 25 to 28, after the establishment of hepatocellular carcinoma. KEY FINDINGS: Spirulina inhibited HCC structural and functional alterations, manifested by improving the survival rate, significantly decreasing the tumor marker AFP, and the count and size of the hepatic nodules, as well as downstaging HCC. This was accompanied with the augmentation of the endogenous antioxidant capacity, apoptosis (Bax) and the tumor suppressor protein (p53), as well as the suppression of tissue levels of the lipid peroxidation marker (MDA) and neoangiogenesis marker (VEGF). SIGNIFICANCE: In conclusion, spirulina has an anticarcinogenic effect against advanced hepatocellular carcinoma exerted through activating the tumor suppressor protein p53 and apoptosis, and suppressing oxidative stress and angiogenesis.