naphthoquinones and Papilloma

In continuation of our studies with chemoprevention potential of plant-derived naphthoquinone derivatives, leaf powder of the medicinal plant Lawsonia inermis L, commonly known as 'henna', was evaluated by its inhibition of the Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Lawsone (2-hydroxy- 1,4-naphthoquinone), the reddish orange pigment artifact formed during the extraction or preparation of the dye from henna leaves and believed to be the active component, was also assessed in this in vitro assay. Both showed a profound inhibition (>88%) of EBV-EA activation. In the in vivo two-stage mouse skin carcinogenesis study using UV-B radiation for initiation and TPA for tumor promotion, oral feeding of henna (0.0025%) in drinking water ad libitum decreased tumor incidence by 66% and multiplicity by 40% when compared to the positive control at 10 weeks of treatment. Similarly, in the above mouse model, orally fed lawsone (0.0025%) decreased tumor incidence by 72% and multiplicity by 50%. The tumor inhibitory trend continued throughout the 20-week test period. Similar antitumor activities were observed when henna (0.5 mg/ml) was applied topically on the back skin in the UV-B initiated, TPA promoted and peroxynitrite initiated, TPA promoted mouse skin carcinogenesis models. Topically applied lawsone (0.015 mg/ml) also exhibited similar protection against tumor formation in the 7,12-dimtehylbenz(a)anthracene induced and TPA promoted skin cancer in mice. Also, there was a delay of 1 to 2 weeks in tumor appearance in both henna and lawsone treated groups compared to control in all three test models. This study ascertains the skin cancer chemopreventive activity of henna leaf powder and lawsone when administered by either oral (through drinking water) or topical (by application on the back skin) routes. Further, it emphasizes the need for the evaluation of these henna-derived green chemopreventive candidates in combination with currently used sunscreen agents for complementary anticancer potential against UV-induced skin carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Cutaneous; Administration, Oral; Animals; Antigens, Viral; Antineoplastic Agents, Phytogenic; B-Lymphocytes; Carcinogenesis; Cell Line, Tumor; Female; Herpesvirus 4, Human; Humans; Lawsonia Plant; Male; Naphthoquinones; Papilloma; Plant Extracts; Plant Leaves; Skin Neoplasms; Tetradecanoylphorbol Acetate; Ultraviolet Rays

As a part of screening studies for cancer chemopreventive agents (anti-tumor promoters), six natural and four synthetic naphthoquinones and five of their analogs were tested for their inhibitory activities against Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. Some of the 1,4-naphthoquinones and their analogs were found to show remarkably potent activities, without showing any cytotoxicity. 1,4-Furanonaphthoquinone (5) and its analog (9) isolated from Avicennia plants (Avicenniaceae), having an alcoholic OH group on the dihydrofuran-ring, displayed the most potent activity. Furthermore, avicenol-A (9) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The result of the present investigation indicated that some of these 1,4-naphthoquinones and their analogs might be valuable as potent cancer chemopreventive agents.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents; Antigens, Viral; Carcinogens; Female; Humans; In Vitro Techniques; Mice; Mice, Inbred ICR; Naphthoquinones; Papilloma; Plant Extracts; Plants, Medicinal; Skin Neoplasms; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Virus Activation

In continuation of our studies of natural and synthetic products as cancer chemopreventive agents, we have examined a number of naphthoquinone derivatives including monomeric, dimeric and tetrameric naphthaquinones occurring in the Diospyros and other selected plant genera. Several synthetic naphthoquinones were also evaluated. Initially these compounds were tested for in vitro anti-tumor promoting effect on Epstein-Barr virus early antigen activation produced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and thereafter in in vivo on two-stage mouse skin carcinogenesis. Our studies show some of these compounds have potent anti-tumor promoting activity.

Topics: Animals; Antigens, Viral; Carcinogens; Cells, Cultured; Female; Mice; Mice, Inbred ICR; Naphthoquinones; Papilloma; Skin Neoplasms; Tetradecanoylphorbol Acetate