Apoptosis of non-small-cell lung cancer cell lines after paclitaxel treatment involves the BH3-only proapoptotic protein Bim
- 15 February 2005
- journal article
- Published by Springer Nature in Cell Death & Differentiation
- Vol. 12 (3) , 292-303
- https://doi.org/10.1038/sj.cdd.4401554
Abstract
A significant variation in susceptibility to paclitaxel-mediated killing was observed among a panel of short-term cultured non-small-cell lung cancer (NSCLC) cell lines. Susceptibility to killing by paclitaxel correlated with expression of the BH3-only protein, Bim, but not with other members of Bcl-2 family. NSCLC cell lines with the highest level of Bim expression are most susceptible to apoptosis induction after paclitaxel treatment. Forced expression of Bim increased paclitaxel-mediated killing of cells expressing an undetectable level of Bim. Conversely, knock down of Bim, but not Bcl-2 expression, decreased the susceptibility of tumor cells to paclitaxel-mediated killing. Similar observations were made using a panel of breast and prostate cancer cell lines. Paclitaxel impairs microtubule function, causes G2/M cell cycle blockade, mitochondria damage, and p53-independent apoptosis. These results established Bim as a critical molecular link between the microtubule poison, paclitaxel, and apoptosis.Keywords
This publication has 57 references indexed in Scilit:
- p38 Mitogen-Activated Protein Kinase Mediates Cell Death and p21-Activated Kinase Mediates Cell Survival during Chemotherapeutic Drug-induced Mitotic ArrestMolecular Biology of the Cell, 2003
- Activation of ERK1/2 by ΔRaf-1 : ER* represses Bim expression independently of the JNK or PI3K pathwaysOncogene, 2003
- Mitochondrial dysfunction is an essential step for killing of non-small cell lung carcinomas resistant to conventional treatmentOncogene, 2002
- A Multistep Model for Paclitaxel-Induced Apoptosis in Human Breast Cancer Cell LinesExperimental Cell Research, 2001
- Paclitaxel Induces Prolonged Activation of the Ras/MEK/ERK Pathway Independently of Activating the Programmed Cell Death MachineryJournal of Biological Chemistry, 2001
- Defective caspase-3 relocalization in non-small cell lung carcinomaOncogene, 2001
- Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and DeathScience, 2001
- Hypoxia induces the expression of the pro-apoptotic gene BNIP3Cell Death & Differentiation, 2001
- Differential Sensitivity of Breast Cancer Cells to Tumor Necrosis Factor-α: Involvement of Protein Kinase CBiochemical and Biophysical Research Communications, 2001
- Bcl-2–Mediated Drug ResistanceThe Journal of Experimental Medicine, 1999