Cancer chemopreventive potential of volatile oil from black cumin seeds, Nigella sativa L., in a rat multi-organ carcinogenesis bioassay

Abstract

Nigella sativa (N. sativa) is a herbal plant of the Ranunculaceae family that has been widely used for various medicinal and nutritional purposes. Volatile oil extracts along with its major constituents, such as thymoquinone, have recently attracted considerable attention for their antioxidant, immunoprotective and antitumor properties. The present study was conducted to assess the chemopreventive potential of crude oils in N. sativa on tumor formation using a well-established rat multi-organ carcinogenesis model featuring initial treatment with five different carcinogens. Post-initiation administration of 1000 or 4000 ppm N. sativa volatile oil in the diet of male Wistar rats for 30 weeks significantly reduced malignant and benign colon tumor sizes, incidences and multiplicities. The treatment also significantly decreased the incidences and multiplicities of tumors in the lungs and in different parts of the alimentary canal, particularly the esophagus and forestomach. Bromodeoxyuridine labeling indices, reflecting cell proliferation were significantly decreased in various organs and lesions after treatment with the two doses of N. sativa. The plasma levels of insulin growth factor, triglycerides and prostaglandin E2 were also altered. The findings show, for the first time, that N. sativa administration exerts potent inhibitory effects on rat tumor development and on cellular proliferation in multiple organ sites. In particular, the ability to significantly inhibit murine colon, lung, esophageal and forestomach tumors was demonstrated in the post-initiation phase, with no evidence of clinical side effects. The mechanisms are likely to be related to suppression of cell proliferation.

Figure 1

Experimental design. Bold arrows, DEN (diethylnitrosamine) 100 mg/kg i.p. Black arrowheads, MNU (N-methylnitrosamine) 20 mg/kg i.p. Black dotted squares, BBN (N-butyl-N-(4-hydroxybutyl)nitrosamine. Grey dotted squares, DHPN (2,2′-dihydroxy-di-N-propylnitrosamine 0.1%) in drinking water. White arrowheads, DMH (dimethylhydrazine), 40 mg/kg s.c. S, sacrifice and blood analysis. Normal arrows, saline 0.9%.

Figure 2

Growth curves of rats in all experimental groups.

Figure 3

IHC data for the numbers (numbers/cm²) and areas (mm²/cm²) of GST-P-positive foci in the rat livers in the test groups.

Figure 4

Serum levels of IGF-I, PGE-2, TG and cholesterol of rats in the test groups. ^*Significantly different vs. the other investigated groups at P<0.05.