Inhibitory effect of black tea on the growth of established skin tumors in mice: effects on tumor size, apoptosis, mitosis and bromodeoxyuridine incorporation into DNA.
Female CD-1 mice were initiated with a single topical application of 7,12-dimethylbenz[a]anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate. Mice with established papillomas were then treated with black tea or decaffeinated black tea (approximately 4 mg tea solids/ml) as the sole source of drinking fluid for 11-15 weeks. In four separate experiments, oral administration of black tea inhibited the growth of papillomas (increase in tumor volume/mouse) by an average of 35%, 37%, 41% and 48%, respectively. Studies with decaffeinated black tea gave inconsistent results. In one experiment, administration of decaffeinated black tea inhibited papilloma growth (increase in tumor volume/mouse) by 27%, but in two additional experiments papilloma growth was stimulated by 14% and 193%, respectively. In a separate experiment, skin tumors were generated by treating SKH-1 female mice with ultraviolet B light (UVB; 30 mJ/cm2) twice weekly for 22 weeks, after which UVB administration was stopped. Tumors were allowed to develop during the following 13 weeks, and tumor-bearing mice were then treated with black tea (6 mg/ml tea solids) as the drinking fluid for 11 weeks. In this experiment, tumor growth (increase in tumor volume/mouse) was inhibited by 70%. Histological examination revealed that tea-treated mice had a 58% decrease in the number of nonmalignant tumors (primarily keratoacanthomas)/mouse and a 54% decrease in the number of squamous cell carcinomas/mouse. In addition, administration of black tea decreased the volume per tumor by 60% for nonmalignant tumors and by 84% for carcinomas. Mechanistic studies with tumors from these mice revealed that administration of black tea decreased the bromodeoxyuridine labeling index in squamous cell papillomas, keratoacanthomas and squamous cell carcinomas by 56%, 45% and 35%, respectively, and the apoptosis index was increased by 44%, 100% and 95%, respectively. Administration of black tea decreased the mitotic index in keratoacanthomas and squamous cell carcinomas by 42% and 16%, respectively. The results indicate that oral administration of black tea to tumor-bearing mice inhibited proliferation and enhanced apoptosis in nonmalignant and malignant skin tumors.
Lu
Y P
YP
Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway 08855-0789, USA.
Lou
Y R
YR
Xie
J G
JG
Yen
P
P
Huang
M T
MT
Conney
A H
AH
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D017209:Apoptosis; D001973:Bromodeoxyuridine / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D004247:DNA / Q000096:biosynthesis*; D005260:Female; D007636:Keratoacanthoma / Q000628:therapy; D051379:Mice; D008938:Mitosis; D010212:Papilloma / Q000628:therapy; D012878:Skin Neoplasms / Q000473:pathology / Q000628:therapy*; D013662:Tea; D014466:Ultraviolet Rays
D013662:Tea; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D001973:Bromodeoxyuridine