Down-regulation of c-Ki-ras2 gene expression associated with morphologic differentiation in human embryonal carcinoma cells treated with berberine.
A pluripotent human embryonal carcinoma (EC) clone, NT2/D1, which was derived from the Tera-2 cell line, was induced to differentiate into cells with neuronal-like cell morphology by treatment with berberine, an alkaloid derived from a Chinese herbal medicine (Huang Lien). As early as one day after 24-hour treatment of cells with berberine at a nontoxic dose of 0.1 mg/ml in culture medium, the cells started to show morphologic changes, developing into terminally differentiated neuronal-like cells with long, inter-connecting network cellular structures. This process was much faster as compared with that induced by treatment with retinoic acid (RA), which took at least several days to develop. Unlike RA, berberine could not induce murine EC cell line, F9, to differentiate into endodermal cells. It was also found that although the NT2/D1 cell clone exhibited amplification and enhanced mRNA expression of c-Ki-ras2 gene as did the parent cell line, a marked down-regulation of c-Ki-ras2 mRNA expression was observed. However, there was no change in actin mRNA expression even after differentiation had occurred. Thus, morphologic differentiation of EC cells into neuronal-like cells was found to be associated with down-regulation of a protooncogene which plays some definite role in oncogenesis. The mechanism by which berberine induces differentiation in these cells needs further investigation.
Laboratory of Cellular Oncology, National Cancer Institute, NIH, Bethesda, MD.
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D000199:Actins / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D011905:Genes, ras; D006801:Humans; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013724:Teratoma / Q000235:genetics / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000199:Actins; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D001599:Berberine; D014212:Tretinoin