| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Gesellschaft für Biotechnologische Forschung mbH, Arbeitsgruppe Immunbiologie [P. F. M.] and Abteilung Naturstoffbiologie [F. S.], Mascheroder Weg 1, D-38124 Braunschweig, Germany
Epothilones are a new class of potential antitumor compounds that were isolated from the myxobacterium Sorangium cellulosum. Epothilones have effects on the cytoskeleton similar to those of the antineoplastic drug Taxol. Both compounds inhibit cell proliferation by stabilizing microtubuli, and they compete for the same binding site. In addition, Taxol displays endotoxin-like properties in that it activates macrophages to synthesize proinflammatory cytokines and nitric oxide. We measured nitric oxide release by IFN-
-treated murine macrophages as an indicator of macrophage activation by epothilone B. Although epothilone B showed the expected effects on the microtubuli, there was no indication of macrophage stimulatory activity by epothilone B, nor did epothilone B inhibit lipopolysaccharide-mediated nitric oxide release. We conclude that, unlike Taxol, epothilone-mediated microtubuli stabilization does not trigger endotoxin-signaling pathways. Moreover, because the endotoxin-like activity of Taxol may be the cause of some nonhematological clinical side effects, it is to be expected that such effects may not occur with epothilones.
1 To whom requests for reprints should be addressed. E-mail, pfm@GBF-Braunschweig.de.
2 The abbreviation used is: LPS, lipopolysaccharide.
Received 5/ 6/97. Accepted 7/ 2/97.
This article has been cited by other articles:
|
|
 |
|
  K. P. Crume, J. H. Miller, and A. C. La Flamme Peloruside A, an Antimitotic Agent, Specifically Decreases Tumor Necrosis Factor-{alpha} Production by Lipopolysaccharide-Stimulated Murine Macrophages Experimental Biology and Medicine, May 1, 2007; 232(5): 607 - 613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lim, T.-J. Kim, Y.-R. Jin, D.-W. Kim, J.-S. Kwon, J.-H. Son, J.-C. Jung, M. A. Avery, D. J. Son, J. T. Hong, et al. Epothilone B Inhibits Neointimal Formation after Rat Carotid Injury through the Regulation of Cell Cycle-Related Proteins J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 648 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Lin, L. Catley, R. LeBlanc, C. Mitsiades, R. Burger, Y.-T. Tai, K. Podar, M. Wartmann, D. Chauhan, J. D. Griffin, et al. Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo Blood, January 1, 2005; 105(1): 350 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Abraham, M. Agrawal, S. Bakke, A. Rutt, M. Edgerly, F. M. Balis, B. Widemann, L. Davis, B. Damle, D. Sonnichsen, et al. Phase I Trial and Pharmacokinetic Study of BMS-247550, an Epothilone B Analog, Administered Intravenously on a Daily Schedule for Five Days J. Clin. Oncol., May 1, 2003; 21(9): 1866 - 1873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-P. H. Yang and S. B. Horwitz Taxol Mediates Serine Phosphorylation of the 66-kDa Shc Isoform Cancer Res., September 1, 2000; 60(18): 5171 - 5178. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. Silakowski, H. U. Schairer, H. Ehret, B. Kunze, S. Weinig, G. Nordsiek, P. Brandt, H. Blocker, G. Hofle, S. Beyer, et al. New Lessons for Combinatorial Biosynthesis from Myxobacteria. THE MYXOTHIAZOL BIOSYNTHETIC GENE CLUSTER OF Stigmatella aurantiaca DW4/3-1 J. Biol. Chem., December 24, 1999; 274(52): 37391 - 37399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-Y. Perera, J. F. Kadow, C. R. Fairchild, K. A. Johnston, and S. N. Vogel Analysis of structure activity relationships for LPS-mimetic activities of taxane analogs in murine macrophages Innate Immunity, October 1, 1999; 5(5-6): 261 - 267. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Bhat, P.-Y. Perera, J. M. Carboni, J. Blanco, D. T. Golenbock, T. N. Mayadas, and S. N. Vogel Use of a Photoactivatable Taxol Analogue to Identify Unique Cellular Targets in Murine Macrophages: Identification of Murine CD18 as a Major Taxol-Binding Protein and a Role for Mac-1 in Taxol-Induced Gene Expression J. Immunol., June 15, 1999; 162(12): 7335 - 7342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-C. Chou, X.-G. Zhang, C. R. Harris, S. D. Kuduk, A. Balog, K. A. Savin, J. R. Bertino, and S. J. Danishefsky Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel PNAS, December 22, 1998; 95(26): 15798 - 15802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Sinha, C. F. Barbas III, and R. A. Lerner The antibody catalysis route to the total synthesis of epothilones PNAS, December 8, 1998; 95(25): 14603 - 14608. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-C. Chou, X.-G. Zhang, A. Balog, D.-S. Su, D. Meng, K. Savin, J. R. Bertino, and S. J. Danishefsky Desoxyepothilone B: An efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone B PNAS, August 4, 1998; 95(16): 9642 - 9647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Moasser, L. Sepp-Lorenzino, N. E. Kohl, A. Oliff, A. Balog, D.-S. Su, S. J. Danishefsky, and N. Rosen Farnesyl transferase inhibitors cause enhanced mitotic sensitivity to taxol and epothilones PNAS, February 17, 1998; 95(4): 1369 - 1374. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
