Berberine‐induced apoptosis of human leukemia HL‐60 cells is associated with down‐regulation of nucleophosmin/B23 and telomerase activity

• Published in: International journal of cancer Vol. 81; no. 6; pp. 923 - 929
• Main Authors: Wu, Hsing L., Hsu, Chen Y., Liu, Wen H., Yung, Benjamin Y.M.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 11.06.1999; Wiley-Liss
• Subjects: Antineoplastic agents; Apoptosis - drug effects; Apoptosis - physiology; Berberine - pharmacology; Biological and medical sciences; Cell Division - drug effects; Cell Survival - drug effects; DNA Fragmentation; Dose-Response Relationship, Drug; Gene Expression Regulation, Neoplastic - drug effects; General aspects; HL-60 Cells - cytology; HL-60 Cells - drug effects; HL-60 Cells - physiology; Humans; Kinetics; Medical sciences; Nuclear Proteins - genetics; Pharmacology. Drug treatments; Phosphoproteins - genetics; Telomerase - genetics; Time Factors; Antineoplastic agent; Human; Promyelocytic leukemia; RNA-directed DNA polymerase; Enzyme; Transferases; Acute; Malignant hemopathy; Nucleolus; In vitro; HL60 cell line; Nucleotidyltransferases; Alkaloid; Nucleophosmin; Cell death; Phosphoproteins; Established cell line; Mechanism of action; Nuclear protein; Apoptosis
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(19990611)81:6<923::AID-IJC14>3.0.CO;2-D

The steady‐state level of nucleophosmin/B23 mRNA decreased during berberine‐induced (25μg/ml, 24 to 96 hr) apoptosis of human leukemia HL‐60 cells. A decline in telomerase activity was also observed in HL‐60 cells treated with berberine. A stable clone of nucleophosmin/B23 over‐expressed in HL‐60 cells was selected and found to be less responsive to berberine‐induced apoptosis. About 35% to 63% of control vector–transfected cells (pCR3) exhibited morphological characteristics of apoptosis, while about 8% to 45% of nucleophosmin/B23‐over‐expressed cells (pCR3‐B23) became apoptotic after incubation with 15μg/ml berberine for 48 to 96 hr. DNA extracted from pCR3 cells contained more fragmented DNA than pCR3‐B23 cells during treatment with 15μg/ml berberine for 24 to 48 hr. Our results indicate that berberine‐induced apoptosis is associated with down‐regulation of nucleophosmin/B23 and telomerase activity. We also suggest that nucleophosmin/B23 may play an important role in the control of the cellular response to apoptosis induction. Int. J. Cancer81:923–929, 1999. © 1999 Wiley‐Liss, Inc.