apigenin and Papilloma

Sixteen compounds (1-16) isolated from the flowering whole plant of Ajuga decumbens have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) induction by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), as a primary screening test for antitumor-promoters (potential cancer chemopreventive agents). Five compounds (6, 9, and 12-14) showed strong inhibitory effects on EBV-EA induction. Of these active compounds, two major constituents of this plant, cyasterone (6) and 8-acetylharpagide (13), showed potent antitumor-promoting activities on a mouse-skin in vivo two-stage carcinogenesis procedure, using 7, 12-dimethylbenz[a]anthracene as initiator and TPA as promoter. Further, compound 13 also exhibited potent chemopreventive activity in a mouse pulmonary tumor model.

Topics: 4-Nitroquinoline-1-oxide; Animals; Antineoplastic Agents, Phytogenic; Antiviral Agents; Carcinogens; Female; Glycerol; Herpesvirus 4, Human; Lung Neoplasms; Mice; Mice, Inbred ICR; Papilloma; Plants, Medicinal; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured

This investigation studied the effect of topical application of apigenin on skin tumorigenesis initiated by 7,12-dimethylbenz(a)anthracene (DMBA) and promoted by 12-O-tetradecanoylphorbol-13-acetate (TPA) in SENCAR mice. Apigenin was a potent inhibitor of epidermal ornithine decarboxylase induction by TPA in a dose-dependent manner from 1 to 20 mumol. Two tumorigenesis studies were conducted. In the first study, 20 mumol of apigenin was applied topically and no effect on body weight was observed. By week 33 after DMBA initiation, 48% of DMBA/TPA-treated mice developed carcinomas, while none occurred in DMBA/apigenin/TPA-treated groups. In the second study, doses of 5 and 20 mumol of apigenin were used. The papilloma incidence for 0, 5, and 20 mumol apigenin at 26 weeks after DMBA was 93.3, 58, and 39.3%, and papilloma numbers per mouse were 7.5, 2.5, and 1.8, respectively. Apigenin prolonged by 3 weeks the latency period of tumor appearance. In addition, apigenin significantly inhibited the incidence of carcinoma and the numbers of carcinomas. The incidence of carcinomas per tumor-bearing animal and the ratio of carcinomas/papillomas in two apigenin-treated groups decreased although there were no significant differences between the three groups. These data indicate that apigenin inhibited skin papillomas and showed the tendency to decrease conversion of papillomas to carcinomas.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Chamomile; Cocarcinogenesis; Dose-Response Relationship, Drug; Enzyme Induction; Epidermis; Flavonoids; Mice; Oils, Volatile; Ornithine Decarboxylase; Papilloma; Plants, Medicinal; Skin Neoplasms; Tetradecanoylphorbol Acetate

Topics: Chamomile; Female; Humans; Leukoplakia; Lichen Planus; Lichens; Neoplasms; Papilloma; Vulva; Vulvar Lichen Sclerosus