Chemoprevention by Hippophae rhamnoides: effects on tumorigenesis, phase II and antioxidant enzymes, and IRF-1 transcription factor.
Fruits or berries of Hippophae rhamnoides (sea buckthorn), a rich source of vitamins A, C, and E, carotenes, flavonoids, and microelements such as sulfur, selenium, zinc, and copper, are edible and have been shown to protect from atopic dermatitis, hepatic injury, cardiac disease, ulcer, and atherosclerosis. However, its mechanism of action is not clear. We show that Hippophae inhibits benzo(a)pyrene-induced forestomach and DMBA-induced skin papillomagenesis in mouse. This decrease in carcinogenesis may be attributed to the concomitant induction of phase II enzymes such as glutathione S-transferase and DT-diaphorase and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the mouse liver. This was accompanied by a remarkable induction of the transcription factor interferon regulatory factor-1 in the Hippophae-treated liver. Our results strongly suggest that Hippophae fruit is able to decrease carcinogen-induced forestomach and skin tumorigenesis, which might involve up-regulation of phase II and antioxidant enzymes as well as DNA-binding activity of IRF-1, a known antioncogenic transcription factor causing growth suppression and apoptosis induction for its anticancer effect.
Padmavathi
Bandhuvula
B
Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
Upreti
Meenakshi
M
Singh
Virendra
V
Rao
A Ramesha
AR
Singh
Rana P
RP
Rath
Pramod C
PC
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D031281:Hippophae / Q000737:chemistry*; D050856:Interferon Regulatory Factor-1; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D010936:Plant Extracts; D015127:9,10-Dimethyl-1,2-benzanthracene; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); D005980:Glutathione Reductase; D005982:Glutathione Transferase