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.
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 microl 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 microl 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.
Kapadia
Govind J
GJ
Department of Pharmaceutical Sciences, School of Pharmacy, Howard University, 2300 4th Street, NW, Washington, DC 20059, USA. gkapadia@howard.edu
Azuine
Magnus A
MA
Sridhar
Rajagopalan
R
Okuda
Yoko
Y
Tsuruta
Atsushi
A
Ichiishi
Eiichiro
E
Mukainake
Teruo
T
Takasaki
Midori
M
Konoshima
Takao
T
Nishino
Hoyoku
H
Tokuda
Harukuni
H
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D027461:Beta vulgaris / Q000737:chemistry*; D050859:Betacyanins; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004052:Diethylnitrosamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006898:Hydroxylamines / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D007211:Indoles / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000517:prevention & control*; D051379:Mice; D008813:Mice, Inbred ICR; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D010634:Phenobarbital / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D014466:Ultraviolet Rays
C477506:(+-)-E-4-methyl-2-((E)-hydroxylamino)-5-nitro-6-methoxy-3-hexanamide; D016588:Anticarcinogenic Agents; D050859:Betacyanins; D002273:Carcinogens; D006898:Hydroxylamines; D007211:Indoles; D010936:Plant Extracts; D004052:Diethylnitrosamine; D015127:9,10-Dimethyl-1,2-benzanthracene; C020228:betanin; D013755:Tetradecanoylphorbol Acetate; D010634:Phenobarbital