Berberine-induced morphologic differentiation and down-regulation of c-Ki- ras2 protooncogene expression in human teratocarcinoma cells

• Published in: Cancer letters Vol. 55; no. 2; pp. 103 - 108
• Main Authors: Chang, K.S.S., Gao, C., Wang, L-C.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 03.12.1990; Elsevier
• Subjects: Animals; berberine; Berberine - pharmacology; Biological and medical sciences; Cell Differentiation - drug effects; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; differentiation; Down-Regulation - drug effects; Down-Regulation - genetics; Fundamental and applied biological sciences. Psychology; Gene Amplification; Gene Expression - drug effects; Humans; Ki- ras protooncogene; Mice; Molecular and cellular biology; Oncogenes - genetics; Proto-Oncogenes - genetics; teratocarcinoma; Teratoma - genetics; Teratoma - pathology; Tumor Cells, Cultured; Ki- ras protooncogene; differentiation; teratocarcinoma; berberine; Human; Alkaloid; Teratoma; C-Onc gene; Malignant tumor; Cell differentiation; Gene expression; Male genital diseases; In vitro; Tumor cell
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/0304-3835(90)90018-S

A pluripotent human teratocarcinoma cell clone, NT2 D1 , which was derived from the Tera-2 cell line, was induced to differentiate into cells with neuronal cell morphology by treatment with berberine. As early as 1 day after a 24-h treatment of cells with berberine at a non-toxic dose of 0.1 mg/ml in culture medium, the cells started to show morphologic changes, developing into terminally differentiated neuronal cells with long, inter-connecting network-like cellular structures. This process is 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 teratocarcinoma cell llne, 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 teratocarcinoma cells into neuronal cells is 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.