Modulatory effect of Morus indica against two-stage skin carcinogenesis in Swiss albino mice: possible mechanism by inhibiting aryl hydrocarbon hydroxylase.
The modulatory effect of the methanolic extract of Morus indica on 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced oxidative stress and 7,12-dimethylbenz(a)anthracene induced and croton oil (0.5% per mouse/0.2 mL acetone, v/v) promoted skin tumourigenesis in Swiss albino mice was studied. The efficacy of the M. indica extract was also evaluated in-vitro by studying the inhibition of the activity and level of aryl hydrocarbon hydroxylase, cytochrome P450, DNA sugar damage in calf thymus DNA and Fe(++)/ascorbate-induced lipid peroxidation in microsomes of mice. Significant increases in the activity of antioxidant enzymes (P <0.001) and a concomitant decrease (P <0.001) in the cutaneous malondialdehyde level were observed at three doses of plant extract (2.5, 5.0 and 7.5 mg kg(-1)). Application of M. indica 1 h before each application of croton oil showed inhibitory effects on tumour promotion in terms of a reduction in the number of tumours/mouse and percentage of mice with tumours. It was also accompanied by an extension of the tumour latency period. TPA, which resulted in a rapid and transient stimulation of mouse epidermal ornithine decarboxylase activity (P <0.001), was inhibited dose dependently by pre-treatment with M. indica extract (P <0.001). The results suggest that M. indica extract may be useful as a therapeutic agent for cancer control as it blocks or suppresses events associated with chemical carcinogenesis.
Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Lakshmi
L
Prasad
Tajdar H
TH
Khan
Anuradha
A
Sehrawat
Sarwat
S
Sultana
D015127:9,10-Dimethyl-1,2-benzanthracene; D000287:Administration, Topical; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D002273:Carcinogens; D003436:Croton Oil; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D031625:Morus / Q000737:chemistry*; D065108:Ornithine Decarboxylase Inhibitors; D018384:Oxidative Stress; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D010936:Plant Extracts; D015127:9,10-Dimethyl-1,2-benzanthracene; D003436:Croton Oil; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D013755:Tetradecanoylphorbol Acetate