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.
Prasad
Lakshmi
L
Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Khan
Tajdar H
TH
Sehrawat
Anuradha
A
Sultana
Sarwat
S
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