Chemoprevention of DMBA-induced UV-B promoted, NOR-1-induced TPA promoted skin carcinogenesis, and DEN-induced phenobarbital promoted liver tumors in mice by extract of beetroot

• Published in: Pharmacological research 2003-02, Vol.47 (2), p.141-148
• Main Authors: Kapadia, Govind J., Azuine, Magnus A., Sridhar, Rajagopalan, Okuda, Yoko, Tsuruta, Atsushi, Ichiishi, Eiichiro, Mukainake, Teruo, Takasaki, Midori, Konoshima, Takao, Nishino, Hoyoku, Tokuda, Harukuni
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - antagonists & inhibitors; 9,10-Dimethyl-1,2-benzanthracene - toxicity; Animals; Anticarcinogenic Agents - pharmacology; Beta vulgaris; Beta vulgaris - chemistry; Betacyanins; Betanin; Body Weight - drug effects; Cancer; Carcinogenesis; Carcinogens - antagonists & inhibitors; Carcinogens - toxicity; Chemoprevention; Diethylnitrosamine - antagonists & inhibitors; Diethylnitrosamine - toxicity; Dose-Response Relationship, Drug; Female; Hydroxylamines - antagonists & inhibitors; Hydroxylamines - toxicity; Indoles - pharmacology; Liver Neoplasms, Experimental - chemically induced; Liver Neoplasms, Experimental - prevention & control; Mice; Mice, Inbred ICR; Neoplasms, Radiation-Induced - prevention & control; Phenobarbital - antagonists & inhibitors; Phenobarbital - toxicity; Plant Extracts - pharmacology; Plant Roots - chemistry; Skin Neoplasms - chemically induced; Skin Neoplasms - prevention & control; Tetradecanoylphorbol Acetate - antagonists & inhibitors; Tetradecanoylphorbol Acetate - toxicity; Ultraviolet Rays; Ultraviolet-B
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/S1043-6618(02)00285-2

Our previous studies identified the extract of Beta vulgaris (beetroot), commercially also known as betanin, as a potent cancer chemopreventive agent in both in vitro Epstein–Barr early antigen activation assay and in an in vivo two-stage mouse lung and skin carcinogenesis. To explore this issue further, we have now investigated its cancer chemopreventive potentials in three different chemical carcinogen initiation–promotion experimental tumor models in mice. Following tumor initiation with 390 nmol of 7,12-dimethylbenz(a)anthracene (DMBA) in 100 μl of acetone, the mouse skin tumor promotion with 3430 J/m 2 of ultraviolet light-B (UV-B) as well as splenomegaly was significantly inhibited by oral administration of 0.0025% betanin. At the same dose, betanin also afforded significant protection in the mouse skin cancer model following the topical application of 390 nmol of (±)-(E)-4-methyl-2-[(E)-hydroxyamino]-5-nitro-6-methoxy-3-hexanamide (NOR-1) in 100 μl of acetone and promoted by topical administration of 1.7 nmol of 12- O-tetradecanoylphorbol-13-acetate (TPA). In the two-stage model of hepatocarcinogenesis in mice with N-nitrosodiethylamine (DEN, 30 mg/kg) as the initiator and phenobarbital as the promoter, oral administration of 0.0025% betanin also showed a very significant inhibition of both the incidence and multiplicity of the liver tumors. These findings along with our initial reports suggest that betanin which is a regularly consumed natural product colorant is an effective cancer chemopreventive agent in mice. The most interesting observation is that the cancer chemopreventive effect was exhibited at a very low dose used in the study and thus indicating that beetroot warrants more attention for possible human applications in the control of malignancy.