Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of beta-tubulin (Asp26Glu) and less stable microtubules

Molecular Cancer Therapeutics
Malathi HariLee M Greenberger

Abstract

Resistance to paclitaxel-based therapy is frequently encountered in the clinic. The mechanisms of intrinsic or acquired paclitaxel resistance are not well understood. We sought to characterize the resistance mechanisms that develop upon chronic exposure of a cancer cell line to paclitaxel in the presence of the P-glycoprotein reversal agent, CL-347099. The epidermoid tumor line KB-3-1 was exposed to increasing concentrations of paclitaxel and 5 micromol/L CL-347099 for up to 1 year. Cells grown in 15 nmol/L paclitaxel plus CL-347099 (KB-15-PTX/099) developed 18-fold resistance to paclitaxel and were dependent upon paclitaxel for maximal growth. They grew well and retained resistance to paclitaxel when grown in athymic mice. Cross-resistance (3- to 5-fold) was observed in tissue culture to docetaxel, the novel taxane MAC-321, and epothilone B. Collateral sensitivity (approximately 3-fold) was observed to the depolymerizing agents vinblastine, dolastatin-10, and HTI-286. KB-15-PTX/099-resistant cells did not overexpress P-glycoprotein nor did they have an alteration of [14C]paclitaxel accumulation compared with parental cells. However, a novel point mutation (T to A) resulting in Asp26 to glutamate substitution in class I (M40) b...Continue Reading

References

Feb 22, 1979·Nature·P B SchiffS B Horwitz
Feb 1, 1989·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M J SchiblerF Cabral
Jan 1, 1986·Annals of the New York Academy of Sciences·F R CabralM J Schibler
Sep 28, 1993·Biochemistry·J F DíazJ M Andreu
Aug 14, 1999·The Journal of Biological Chemistry·M L Gonzalez-GarayF Cabral
Feb 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·P GiannakakouT Fojo
Nov 4, 2000·Expert Opinion on Investigational Drugs·C Dumontet
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·J P SnyderE Nogales
Aug 11, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Nov 9, 2001·Journal of Molecular Biology·J LöweE Nogales
Dec 26, 2001·Journal of the National Cancer Institute·M J KelleyD H Harpole
Jan 31, 2002·Annual Review of Medicine·Michael M Gottesman
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Jan 17, 2003·Nature·Alexander PalazzoGregg G Gundersen
Aug 9, 2003·Cell Motility and the Cytoskeleton·Malathi HariFernando Cabral
Oct 25, 2003·Oncogene·George A OrrSusan Band Horwitz
May 4, 2004·Molecular Biology of the Cell·Rajat Bhattacharya, Fernando Cabral

❮ Previous
Next ❯

Citations

May 23, 2007·Cancer Chemotherapy and Pharmacology·Ramesh K RamanathanAllen Cohn
Mar 15, 2011·Cancer Chemotherapy and Pharmacology·Howard R Mellor, Richard Callaghan
Jul 27, 2012·Pharmaceutical Research·Jack A TuszynskiGane Ka-Shu Wong
Jan 11, 2007·Journal of the American Chemical Society·Younkee PaikDavid G I Kingston
Oct 5, 2010·Nature Reviews. Drug Discovery·Charles Dumontet, Mary Ann Jordan
Dec 28, 2007·The New England Journal of Medicine·Kathy MillerNancy E Davidson
Mar 2, 2011·Antimicrobial Agents and Chemotherapy·Raymond F SchinaziJames H Nettles
Dec 9, 2010·Molecular Cancer Therapeutics·Jen-Hsuan Wei, Joachim Seemann
Feb 9, 2008·Pharmacology·Howard R Mellor, Richard Callaghan
Jun 4, 2008·Future Oncology·Stacy L Moulder
Mar 13, 2014·International Journal of Molecular Sciences·Li-Xia FengNa Zhang
May 16, 2014·Nature Communications·Yi-Zhou JiangZhi-Ming Shao
Feb 28, 2009·Women's Health·Cristian VillanuevaXavier Pivot
Dec 14, 2007·Expert Opinion on Therapeutic Targets·Vinay K Singh, Zongchao Jia
May 2, 2008·Expert Opinion on Investigational Drugs·Robert O Carlson
Dec 3, 2014·Biotechnology Advances·Shengpeng WangMeiwan Chen
Nov 17, 2009·Urologic Oncology·William K Kelly
Nov 5, 2014·Journal of Medicinal Chemistry·James H NettlesRaymond F Schinazi
Jun 3, 2008·The Prostate·Norihiro HayashiMartin E Gleave
Jan 10, 2008·International Journal of Cancer. Journal International Du Cancer·Edward W HowardYong Chuan Wong
Jun 28, 2013·Experimental Dermatology·Ayano WatanabeChihaya Maesawa
May 17, 2008·Cancer Letters·Hongbo WangXiaoguang Chen
Mar 5, 2015·Journal of Cellular Biochemistry·Kanika Verma, K Ramanathan
Aug 6, 2015·Nanomedicine·Vaibhav MundraRam I Mahato
Jul 12, 2011·Biochimica Et Biophysica Acta·Anutosh Ganguly, Fernando Cabral

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.