nsc-4347 and Cell-Transformation--Neoplastic

Betel quid chewing is a general oral habit in Taiwan, India, southeastern Asian and South Africa with or without the additive of tobacco, alcohol or lime. In this study, the tumor-promoting neoplastic transformation effect of Lime-Piper betel quid (LPB) was examined on JB6 cells. The treatment of LPB at a high dose (1.0 mg/ml) for over 5 days or at lower doses (0.1, 0.5 mg/ml) for over 15 days induced the formation of transformed foci. The transformed cells showed the characteristics of colony formation in soft agar, higher growth rate and multilayer on culture dish. A two-fold induction of the protein levels of c-fos and c-jun proto-oncogenes was observed in the cells from the 50th passage (Cl1/p50, Cl2/p50 and Cl3/p50), suggesting that LPB-transformed cells were oncogenic. In addition, the LPB-transformed cells possessed an elevated level of c-Myc and an increased cell population distributed in the S phase of the cell cycle. These results demonstrated the promotion effect of LPB and indicate that it could be a tumor promoter.

Topics: Alkaloids; Areca; Blotting, Western; Calcium Compounds; Carcinogens; Cell Line; Cell Proliferation; Cell Transformation, Neoplastic; Citrus aurantiifolia; Flow Cytometry; Gene Expression Regulation; Mastication; Oxides; Piper; Piperaceae; Plant Extracts; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Proto-Oncogene Proteins c-myc; S Phase; Taiwan; Time Factors

Betel quid chewing is a general behavior in Taiwan, India, southeastern Asian and South Africa. In this study, microculture tetrazolium test (MTT) showed that the extract of lime-piper betel quid (LPB) (1.0-20 mg/ml) was toxic to JB6 cells. Cells exposed of LPB (0.1, 0.5, 1.0 mg/ml) for 7 days resulted in changes in cytomorphology with characteristics of carcinogenesis. With a long-term treatment (approximately 30 days) of low doses of LPB (1, 5, 10 microg/ml), the production of H2O2 and the activity of myeloperoxidase (MPO) and ornithine decarboxylase (ODC) were increased in JB6 cells. Cell cycle analysis showed a decrease in the G1 phase and an accumulation in the S phase 48 h after LPB treatment. When treating with 0.5 mg/ml LPB for 15 days as a promoter, type III foci were formed in the JB6 culture. These results demonstrated the tumor promotional effect of LPB in JB6 cells.

Topics: Animals; Areca; Calcium Compounds; Carcinogenicity Tests; Carcinogens; Cell Cycle; Cell Line; Cell Transformation, Neoplastic; Citrus aurantiifolia; G1 Phase; Hydrogen Peroxide; Mice; Ornithine Decarboxylase; Oxides; Peroxidase; Piper; Plant Extracts; S Phase; Tetrazolium Salts; Thiazoles