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.

Abstract

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.

• Authors: Govind J Kapadia, Magnus A Azuine, Rajagopalan Sridhar, Yoko Okuda, Atsushi Tsuruta, Eiichiro Ichiishi, Teruo Mukainake, Midori Takasaki, Takao Konoshima, Hoyoku Nishino, Harukuni Tokuda
• Journal: Pharmacological research (Pharmacol Res) Vol. 47 Issue 2 Pg. 141-8 (Feb 2003) ISSN: 1043-6618 [Print] Netherlands
• PMID: 12543062 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• (+-)-E-4-methyl-2-((E)-hydroxylamino)-5-nitro-6-methoxy-3-hexanamide
• Anticarcinogenic Agents
• Betacyanins
• Carcinogens
• Hydroxylamines
• Indoles
• Plant Extracts
• Diethylnitrosamine
• 9,10-Dimethyl-1,2-benzanthracene
• betanin
• Tetradecanoylphorbol Acetate
• Phenobarbital

Topics

• 9,10-Dimethyl-1,2-benzanthracene (antagonists & inhibitors, toxicity)
• Animals
• Anticarcinogenic Agents (pharmacology)
• Beta vulgaris (chemistry)
• Betacyanins
• Body Weight (drug effects)
• Carcinogens (antagonists & inhibitors, toxicity)
• Diethylnitrosamine (antagonists & inhibitors, toxicity)
• Dose-Response Relationship, Drug
• Female
• Hydroxylamines (antagonists & inhibitors, toxicity)
• Indoles (pharmacology)
• Liver Neoplasms, Experimental (chemically induced, prevention & control)
• Mice
• Mice, Inbred ICR
• Neoplasms, Radiation-Induced (prevention & control)
• Phenobarbital (antagonists & inhibitors, toxicity)
• Plant Extracts (pharmacology)
• Plant Roots (chemistry)
• Skin Neoplasms (chemically induced, prevention & control)
• Tetradecanoylphorbol Acetate (antagonists & inhibitors, toxicity)
• Ultraviolet Rays