Aim: Hepatocellular carcinoma (HCC) is a potentially life-threatening cancer. In the current study, anti-HCC efficacy of amygdalin, or metformin alone or in combination in comparison to doxorubicin was studied.
Main methods: Both in-vitro and in-vivo based models. HepG-2 and Huh-7 cell lines as established in-vitro model for HCC were treated with different concentrations of indicated drugs to evaluate the cytotoxicity and determine IC50 for 24, 48 and 72 h. Moreover, the effect of different treatments on apoptosis and cell cycle using flow cytometric analysis were studied. Hepatocellular carcinoma induced in rats by diethyl-nitrosamine and carbon tetrachloride was established, to further investigate the efficacy of indicated drugs. Aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase were measured by spectrophotometer, alpha-fetoprotein, cytochrome-c, caspase-3 and malondialdehyde were measured by ELISA, and liver biopsies were also evaluated histopathologically.
Key findings: In-vitro results showed that the combination has a promising effect when compared to amygdalin or metformin alone as it is more cytotoxic and have higher ability for induction of apoptosis and arresting cell cycle. In-vivo doxorubicin has a good effect for treating HCC. Also, the combination showed a promising prognostic effect depending on the cytotoxic activity and tumor marker when compared to amygdalin or metformin alone.
Significance: Based on the current data, it was hypothesized that amygdalin and metformin especially when used in combination will be a promising approach with low side effects for enhancement of HCC.
Keywords: Amygdalin; Cell cycle; Cytotoxicity apoptosis induction; Doxorubicin; Hepatocellular carcinoma; Metformin.
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