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Please use this identifier to cite or link to this item: http://dspace.library.iitb.ac.in/jspui/handle/10054/4622

Title: Paclitaxel-resistant human ovarian cancer cells undergo c-Jun NH2-terminal kinase-mediated apoptosis in response to noscapine
Authors: ZHOU, J
GUPTA, K
YAO, J
YE, KQ
PANDA, D
GIANNAKAKOU, P
JOSHI, HC
Keywords: human-tumor-cells
protein-kinase
mitotic block
multidrug-resistance
signal-transduction
dynamic instability
beta-tubulin
map kinases
microtubule
taxol
Issue Date: 2002
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation: JOURNAL OF BIOLOGICAL CHEMISTRY, 277(42), 39777-39785
Abstract: We have previously discovered the opium alkaloid noscapine as a microtubule interacting agent that binds to tubulin, alters the dynamics of microtubule assembly, and arrests mammalian cells at mitosis (Ye, K., Ke, Y., Keshava, N., Shanks, J., Kapp, J. A., Tekmal, R. R., Petros, J., and Joshi, H. C. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 1601-1606; Ye, K., Zhou, J., Landen, J. W., Bradbury, E. M., and Joshi, H. C. (2001) J. BioL Chem. 276, 46697-46700; Zhou, J., Panda, D., Landen, J. W., Wilson, L., and Joshi, H. C. (2002) J. Biol. Chem. 277, 17200-17208). Here we show that noscapine does not compete with paclitaxel for tubulin binding and can efficiently inhibit the proliferation of both paclitaxel-sensitive and paclitaxel-resistant human ovarian carcinoma cells (i.e. the parental cell line 1A9 and two derivative cell lines, 1A9PTX10 and 1A9PTX22, which harbor beta-tubulin mutations that impair paclitaxel-tubulin interaction (Giannakakou, P., Sackett, D. L., Kang, Y. K., Zhan, Z., Buters, J. T., Fojo, T., and Poruchynsky, M. S. (1997) J. Biol. Chem. 272,17118-17125). Strikingly, these cells undergo apoptotic death upon noscapine treatment, accompanied by activation of the c-Jun NH2-terminal kinases (JNK). Furthermore, inhibition of JNK activity by treatment with antisense oligonucleotide or transfection with dominant-negative JNK blocks noscapine-induced apoptosis. These findings thus indicate a great potential for noscapine in the treatment of paclitaxel-resistant human cancers. In addition, our results suggest that the JNK pathway plays an essential role in microtubule inhibitor-induced apoptosis.
URI: http://dx.doi.org/10.1074/jbc.M203927200
http://dspace.library.iitb.ac.in/xmlui/handle/10054/4622
http://hdl.handle.net/10054/4622
ISSN: 0021-9258
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