Protective and therapeutic effects of cannabis plant extract on liver cancer induced by dimethylnitrosamine in mice

Hepatocellular carcinomas will emerge as a major form of malignancy in the coming decades. When these tumors are in advanced stages, few therapeutic options are available. Therefore, it is essential to search for new treatment modalities to fight this disease.Aim: Evaluate the possible protective and therapeutic effects of Cannabis extract on dimethylnitrosamine (DMNA)-induced hepatocarcinogenicity in mice.Methods: Seventy-five male mice were divided into five groups of 15 each: group I mice received corn oil only as the control group; group II mice were injected intraperitoneally with DMNA (10 lg/kg body weight) weekly for 12 weeks; group III mice were pretreated orally with cannabis extract (0.5 ml/kg body weight) every other day for two weeks before the injection of DMNA, and continued until the end of the experiment (12 weeks); group IV mice were treated orally with cannabis extract every other day simultaneously with DMNA injection and continued until the end of the experiment; group V mice were treated orally with cannabis extract every other day after receiving the last intraperitoneal injection of DMNA. A real time PCR was used to quantify telomerase reverse transcriptase and caspase-8 m-RNA expression level. Results: As compared to the control group, mTERT mRNA expression level was significantly increased in group II. The gene in groups (III, IV, and V) was insignificantly higher than the control group but it was significantly decreased as compared to group II. The caspase-8 mRNA expression level was significantly decreased in all groups as compared to the control group. As compared to group II, caspase-8 mRNA level was significantly increased in group III. Conclusion: The protective effect of cannabis extract is more pronounced in group taking cannabis before DMNA. Cannabinoids might exert their anti-tumor effects by the direct induction of apoptosis and can decrease telomerase activity by inhibiting the expression of the TERT gene. Coordination between inhibition of telomerase activity and induction of apoptosis might be a potential therapeutic agent for cancer treatment. KEYWORDS Hepatocellular carcinoma; Cannabis; mTERT; Caspase-