Activation of CDC 25 phosphatase and CDC 2 kinase involved in GL331-induced apoptosis

CDC 25 is a dual phosphatase responsible for dephosphorylation and, thus, activation of CDC 2 kinase in G2. Abnormal activation of cyclin B-associated CDC 2 kinase has been implicated in apoptosis induced by cancer chemotherapeutic agents such as paclitaxel (Taxol) and etoposide (VP-16). In this stu...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-07, Vol.57 (14), p.2974-2978
Main Authors: HUANG, T.-S, SHU, C.-H, YANG, W. K, WHANG-PENG, J
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents, Phytogenic - pharmacology
Apoptosis - drug effects
Biological and medical sciences
CDC2 Protein Kinase - drug effects
cdc25 Phosphatases
Cell Cycle Proteins - drug effects
Enzyme Activation
General aspects
Humans
Medical sciences
Oligonucleotides, Antisense - pharmacology
Pharmacology. Drug treatments
Phosphoprotein Phosphatases - drug effects
Podophyllotoxin - pharmacology
Tumor Cells, Cultured
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Summary:CDC 25 is a dual phosphatase responsible for dephosphorylation and, thus, activation of CDC 2 kinase in G2. Abnormal activation of cyclin B-associated CDC 2 kinase has been implicated in apoptosis induced by cancer chemotherapeutic agents such as paclitaxel (Taxol) and etoposide (VP-16). In this study, we found that the CDC 2 kinase could be transiently activated when nasopharyngeal carcinoma NPC-TW01 cells were treated for 3 h with a new anticancer agent, GL331. GL331 treatment also induced a concomitant increase in CDC 25A phosphatase activity and a reduced level of Tyr-15-phosphorylated CDC 2 in NPC-TW01 cells. Furthermore, subsequent apoptotic DNA fragmentation induced by GL331 could be interrupted by treatment of the cells with the cyclin B1-specific antisense oligonucleotides, suggesting that abnormal activation of cyclin B1-associated CDC 2 kinase and CDC 25A phosphatase was involved in GL331-induced apoptosis. Raf-1 has been shown to associate with CDC 25A and, thus, to stimulate its phosphatase activity. Our results revealed that GL331 could facilitate the association of CDC 25A with Raf-1, resulting in the cascade of CDC 25A phosphatase activation and CDC 2 kinase activation, as well as related signaling pathways, and ultimately causing apoptosis in cancer cells.
ISSN:0008-5472
1538-7445