TAILIEUCHUNG - Báo cáo khoa học: Distinct signaling pathways of microtubule inhibitors – vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms, respectively

Vinblastine and paclitaxel (Taxol) are widely used chemotherapeutic drugs that inhibit the normal function of microtubules causing mitotic arrest and cell death. Despite these similarities, the signaling pathways that mediate and regulate cell death induced by these agents remain incompletely under-stood. | ỊFEBS Journal Distinct signaling pathways of microtubule inhibitors -vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms respectively Sergey N. Kolomeichuk1 David T. Terrano1 Christopher S. Lyle1 Kanaga Sabapathy2 and Timothy C. Chambers1 1 Department of Biochemistry and Molecular Biology University of Arkansas for MedicalSciences Little Rock AR USA 2 Laboratory of Molecular Carcinogenesis NationalCancer Center Singapore Keywords apoptosis c-Jun AP-1 JNK Taxol vinblastine Correspondence T. Chambers Department of Biochemistry and Molecular Biology University of Arkansas for Medical Sciences Mail Slot 516 4301 W. Markham St Little Rock AR 72205-7199 USA Fax 1 501 686 8169 Tel 1 501 686 5755 E-mail chamberstimothyc@ Received 22 December 2007 revised 14 February 2008 accepted 20 February 2008 doi Vinblastine and paclitaxel Taxol are widely used chemotherapeutic drugs that inhibit the normal function of microtubules causing mitotic arrest and cell death. Despite these similarities the signaling pathways that mediate and regulate cell death induced by these agents remain incompletely understood. The purpose of this study was to directly compare the two drugs in terms of their ability to activate components of the c-Jun N-terminal protein kinase JNK pathway and to establish the importance of these signaling events in apoptosis induced by these agents. We show that both drugs induce mitotic arrest and subsequent apoptotic cell death with highly similar kinetics and that both activate JNK and induce c-Jun protein and c-jun mRNA expression. Surprisingly vinblastine induced c-Jun phosphorylation and c-jun transcriptional activation although Taxol failed to do so. However inhibition of JNK or an absence of JNK protected against both vinblastine- and Taxol-induced cell death. These results suggest that although JNK activation plays an important role in cell death induced by .

• Báo cáo khoa học
• Report medicine
• traditional medicine
• scientific reports
• immune system
• Antimicrobial
• biosynthesis
• medical knowledge
• medical research
• analysis of cytoplasmic
• oxidation
• Crystal structure
• bacteria
• hemoglobin
• medicine
• cell proliferation
• breast cancer
• chemical reaction
• gastric cancer
• hormone medicine
• tumor cells
• biochemical studies
• environmental medicine