Chemopreventive effect of resveratrol, sesamol, sesame oil and sunflower oil in the Epstein-Barr virus early antigen activation assay and the mouse skin two-stage carcinogenesis.
Resveratrol, sesamol, sesame oil and sunflower oil are known natural dietary components with intrinsic cancer chemopreventive potentials. As a part of our study of dietary constituents as potential cancer chemopreventive agents, we have assessed the anti-cancer potentials of these products in the promotion stage of cancer development employing the in vitro Epstein-Barr virus early antigen activation assay induced by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, we studied the activities of these compounds in the brine shrimp cytotoxicity assay as well as on the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging bioassay with a view to comparing some of the mechanisms of their anti-cancer activity. Finally, we compared the observed chemoprotective capabilities of the four products in the in vivo 7,12 dimethylbenz(a)anthracene initiated and TPA-promoted mouse skin two-stage carcinogenesis protocols. All the products tested showed a profound inhibitory effect on the Epstein-Barr virus early antigen induction using Raji cells. Comparatively, sesame oil was the most potent followed by sesamol and then resveratrol. Only sesamol and resveratrol showed a remarkable cytotoxic activity in the brine shrimp lethality assays as well as profound free radical scavenging activity in the DPPH bioassay. In both test systems, sesamol exhibited a more remarkable activity than resveratrol while sesame oil and sunflower oil did not exhibit any appreciable activity even at the highest concentrations tested (4000 microg ml(-1) ). In our in vivo assay at a 50-fold molar ratio to TPA, sesamol offered 50% reduction in mouse skin papillomas at 20 weeks after promotion with TPA. Under an identical molar ratio to TPA, resveratrol offered a 60% reduction in the papillomas in mouse at 20 weeks. Thus sesamol seems to be an almost equally potent chemopreventive agent. Sesame oil and sunflower oil offered 20 and 40% protection, respectively, in the mouse skin tumor model. The anti-oxidant capabilities of these compounds could not solely explain the observed anti-cancer characteristics. Resveratrol is present in grapes. Sesamol, a constituent of sesame oil and sunflower oil are regularly consumed dietary natural products. The observed chemopreventive effect of these products particularly warrants more attention since they already exist in the population with no known adverse effects.
Kapadia
Govind J
GJ
Laboratory of Natural Drug Products, Department of Pharmaceutical Sciences, School of Pharmacy, Howard University, 2300 4th Street NW, Washington, DC 20059, USA. gkapadia@howard.edu
Azuine
Magnus A
MA
Tokuda
Harukuni
H
Takasaki
Midori
M
Mukainaka
Teruo
T
Konoshima
Takao
T
Nishino
Hoyoku
H
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D001156:Artemia / Q000187:drug effects*; D052117:Benzodioxoles; D001713:Biphenyl Compounds; D003043:Cocarcinogenesis; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D007928:Lethal Dose 50; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D010851:Picrates; D010938:Plant Oils / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D000077185:Resveratrol; D012715:Sesame Oil / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D000074242:Sunflower Oil; D013755:Tetradecanoylphorbol Acetate; D014407:Tumor Cells, Cultured; D014775:Virus Activation / Q000187:drug effects*
D000956:Antigens, Viral; D000972:Antineoplastic Agents, Phytogenic; D052117:Benzodioxoles; D001713:Biphenyl Compounds; C033305:Epstein-Barr virus early antigen; D016166:Free Radical Scavengers; D010636:Phenols; D010851:Picrates; D010938:Plant Oils; D013267:Stilbenes; D000074242:Sunflower Oil; D015127:9,10-Dimethyl-1,2-benzanthracene; D012715:Sesame Oil; C025583:sesamol; C004931:1,1-diphenyl-2-picrylhydrazyl; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol