Anticancer activity of thymoquinone and its combinations with doxorubicin and linseed oil in the treatment of xenograft tumors

Thymoquinone (TQ), the main bioactive component of Nigella sativa, has shown promising anticarcinogenic activity in extensive preclinical studies. This study aimed to evaluate the antitumor activity of TQ, in a wide range of doses with monotherapy and combined use with known the chemotherapeutic drug doxorubicin (Dox) and linseed oil (LO) in a rat model with Pliss lymphosarcoma (PLS) and a mouse model with Lewis lung adenocarcinoma (LLC). Animals was administered orally of TQ daily for 12 days at doses of 5, 10 and 30 mg/kg of body weight (rats) and 5 mg/kg (mice) from the 7th day after subcutaneous transplantation of tumors, as well as combinations of TQ with Dox (5 mg/kg, once at the start of treatment by i.p.) and LO (3 ml/kg, orally). It was found that TQ in the studied doses significantly suppresses the growth of the PLS and the LLC tumors (p < 0.001) and increases the frequency of complete tumor regression (FCR) (p < 0.001) compared to control. TQ, especially (TQ + LO) were able to effectively potentiates the antitumor effect of Dox when used in combination, reducing the PLS tumor volume at the end of treatment by 1.9-2.7 times (p < 0.009), increasing the FCR tumors 60 days after the start of treatment by 2.7-3.7 times (p < 0.02) (PLS) and by 1.5 times (p <= 0.05) (LLC), as well as reducing the LLC frequency of metastasis compared to Dox monotherapy. The results strongly suggest that TQ and its combination with LO have clinical potential as an adjuvant in cancer chemotherapy using Dox.