Skin tumor promotion by argemone oil/alkaloid in mice: evidence for enhanced cell proliferation, ornithine decarboxylase, cyclooxygenase-2 and activation of MAPK/NF-kappaB pathway.
Consumption of argemone oil (AO) contaminated edible oil causes "Epidemic Dropsy". Previously, we have shown that AO and isolated sanguinarine possess genotoxicity and skin tumor initiating activity. Here, we evaluate tumor-promoting potential of AO/sanguinarine alkaloid and investigate the molecular mechanisms involved therein. Single topical application of AO (50-400 microl/mouse) or sanguinarine alkaloid (1.5-12.0 micromol/mouse) afforded significant increase in (i) ornithine decarboxylase (ODC) activity, (ii) uptake of [(3)H]-thymidine in DNA, (iii) cyclooxygenase-2 (COX-2), proliferating cell nuclear antigen (PCNA) and ODC protein expressions, (iv) phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-jun-N-terminal kinase (JNK)1/2 and p38 mitogen-activated protein (MAP) kinases, (v) increased NF-kappaB activation and (vi) no significant increase in dark basal keratinocytes. Subsequently, when AO and sanguinarine alkaloid was tested either as complete or stage I or stage II tumor promoter in 7, 12-dimethyl benz(a)anthracene (DMBA)-initiated mice, there was enhanced tumor incidence, tumor body burden and higher % of mice with tumors, when AO (0.1 ml) or isolated sanguinarine (1.5 micromol) was tested as stage II tumor promoter. However, no tumors were found when AO or sanguinarine alkaloid was tested either as complete or stage I tumor promoter. These results indicate that AO/ sanguinarine alkaloid possesses tumor-promoting potential at stage II level involving MAPK/NF-kappaB pathway.
Food Toxicology Division, Indian Institute of Toxicology Research formerly Industrial Toxicology Research Centre, Council for Scientific and Industrial Research, Mahatma Gandhi Marg, PO Box #80, Lucknow 226 001, India. kmansari@iitr.res.in
Kausar M
KM
Ansari
Mukul
M
Das
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000037:antagonists & inhibitors / Q000633:toxicity; D000470:Alkaloids / Q000633:toxicity*; D000818:Animals; D053119:Benzophenanthridines / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D002452:Cell Count; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis*; D016328:NF-kappa B / Q000096:biosynthesis*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity; D010938:Plant Oils / Q000633:toxicity*; D012639:Seeds / Q000737:chemistry / Q000633:toxicity; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology
D000470:Alkaloids; D053119:Benzophenanthridines; D002273:Carcinogens; D007546:Isoquinolines; D016328:NF-kappa B; D010936:Plant Extracts; D010938:Plant Oils; C030610:argemone oil; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; C005705:sanguinarine; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; D009955:Ornithine Decarboxylase