Involvement of Tiam1 in Apoptosis Induced by Bufalin in HeLa Cells

Background: It has been previously demonstrated that bufalin, an active agent in the Chinese medicine chan' su, induces apoptosis in human leukemia cells by altering the expression of apoptosis-related genes, such as bcl-2 and c-myc. Tiam1 was also found to play a critical role in bufalin-induc...

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Published in:Anticancer research 2007-01, Vol.27 (1A), p.245-249
Main Authors: Cao-Hong, Shibayama-Imazu, Toshiko, Masuda, Yutaka, Shinki, Toshimasa, Nakajo, Shigeo, Nakaya, Kazuyasu
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Apoptosis - drug effects
Apoptosis - physiology
Biological and medical sciences
Bufanolides - pharmacology
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Guanine Nucleotide Exchange Factors - biosynthesis
Guanine Nucleotide Exchange Factors - genetics
HeLa Cells
Humans
Medical sciences
Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
RNA, Small Interfering - genetics
T-Lymphoma Invasion and Metastasis-inducing Protein 1
Transfection
Tumors
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Summary:Background: It has been previously demonstrated that bufalin, an active agent in the Chinese medicine chan' su, induces apoptosis in human leukemia cells by altering the expression of apoptosis-related genes, such as bcl-2 and c-myc. Tiam1 was also found to play a critical role in bufalin-induced apoptosis through the activation of the Rac1, PAK and JNK pathway in human leukemia cell lines. In the present study, the involvement of the Tiam1 gene products in bufalin-induced apoptosis in human solid tumor HeLa cells was examined. Materials and Methods: HeLa cells were treated with 10 -8 M bufalin and apoptosis was measured by ELISA quantification of nucleosomes. Tiam1 mRNA levels were quantified by real-time PCR analysis and inhibited by transfected siRNA specific for Tiam1. Results: Apoptosis was induced in HeLa cells by treatment with 10 -8 M bufalin. Expression of both Tiam1 mRNA and its protein was induced 0.5 h after the start of the bufalin treatment. Transfection of Tiam1-specific siRNA into HeLa cells markedly inhibited bufalin-induced apoptosis. Conclusion: Our results suggest that Tiam1 is a downstream mediator of bufalin-induced apoptosis in the human solid tumor HeLa cell line, as well as in leukemia cell lines.
ISSN:0250-7005
1791-7530