Drug-Resistant Cells

O. Rixe, W. Ortuzar, M. Alvarez, R. Parker, E. Reed, K. Pauli, T. Fojo, Oxaliplatin, Tet-raplatin, Cisplatin, and Carboplatin Spectrum of Activity in Drug-Resistant Cell Lines and in the Cell Lines of the NCI s Anticancer Drug Screen Panel , Biochem. Pharmacol. 1996, 52, 1855 - 1865. 

Based on the same principle of modulation of drug absorption, other less known botanicals could produce similar or different effects compared to St. John s wort. Rosemary (Rosemarinus officinalis Labiatae) is a commonly used dietary botanical that has been found to have a chemopreventive effect (24). Furthermore, in drug-resistant MCF-7 human breast cancer cells expressing P-glycoprotein, methanol extracts of Rosemary at two concentrations (16.5 and 85 pg/mL) inhibited the efflux and increased intracellular accumulation of doxorubicin and vinblastine, two chemotherapeutic drugs that are known substrates of P-glycoprotein. Treatment of drug-resistant cells with the extracts also increased the cytotoxic effects of doxorubicin. On the other hand, in wild-type MCF-7 cells that do not express... 

It is worthy of note that the activity against MCF7-R expressing MDR phenotype is very sensitive to the structure of the C-10 modifier, while this structural variation generally has little effect on the activity against the normal cancer cell lines. The fact clearly indicates that there is no apparent correlation between the activities of the taxoids against the normal cancer cell lines and the drug-resistant cell line. 

Greenberger LM, Lothstein L, Williams SS, et al. Distinct P-glycoprotein precursors are overproduced in independently isolated drug-resistant cell lines. Proc Natl Acad Sci U S A 1988 85(ll) 3762-3766. 

Another approach to modulate drug efflux could be in the treatment of drug-resistant cells with MDR1-targeted siRNAs. Such a treatment resulted in... 

Sorcin 22 5.7 nd nd 4 Drug resistant cells Drug resistance ( ) 58... 

Table 6 Checkerboard microplate method for the two drug-resistant cell lines...

The proteins whose abundances are altered in the plasma membrane in drug-resistant cells (Table 13.2) include those involved in increased amino acid uptake (4F2 cell-surface antigen heavy chain, large neutral amino acids transporter small subunit-1), reduced glucose uptake (stomatin, facilitated glucose transport... 

KavaUaris, M. Burkhart, C. A. Horwitz, S. B. Antisense oligonucleotides to class III beta-tubulin sensitize drug-resistant cells to Taxol. Br. J. Cancer, 1999, 80 1020-1025. 

Rixe O, Ortuzar W, Alvarez M et al. Oxaliplatin, tetraplatin, cisplatin, and carboplatin Spectrum of activity in drug-resistant cell lines and in the cell lines of the National Cancer Institute s Anticancer Drug Screen panel. Biochem Pharmacol 1996 52 1855-65. 

Minderman H, Wrzosek C, Cao S, Utsugi T, Kobunai T, Yamada Y, Rustum YM. Mechanism of action of the dual topoisomerase-I and -II inhibitor TAS-I03 and activity against (multi)drug resistant cells. Cancer Chemother Pharmacol 2000 45(I) 78-84. 

Uterine sarcoma MES-SA is derived from human uterus sarcoma. MES-SA/DX-5 is a multiple drug resistant cell line established from MES-SA cells. These two cell lines are generally used together to study multi-drug resistance and to test modulators to enhance drug delivery across the cell membrane. 

These mutations occur naturally and randomly and do not require the presence of the drug. Indeed, it is likely that a drug-resistant cell is present in a bacterial population even before the drug is encountered. This was demonstrated with the identification of streptomycin-resistant cells from old cultures of a bacterium called E. coli which had been freeze-dried to prevent multiplication before the introduction of streptomycin into medicine. 

Aranda, G. Calcabtinr, A. Meschini, S. Molinati, A. Intracellular distribution of anthracy-clines in drug resistant cells. Cytotechnology 1998, 27, 95-111. 

P-gp mutants isolated from drug-resistant cell lines. Photolabeling with [207, 208]... 

Thierry, A. R., Vige, D., Coughhn, S. S., Belh, J. A., Dritscilo, A., Rahman, A. Modulation of doxorubicin resistance in multi-drug resistant cells by liposomes. FASEB J. 1993, 7, 572—579. 

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