Multidrug resistant cells

Sorcin (soluble resistance-related calcium binding protein) was isolated from multidrug-resistant cells and is expressed in a few mammalian tissues such as skeletal muscle, heart, and brain. In the heart, sorcin interacts with the ryanodine receptor and L-type Ca2+-channels regulating excitation in contraction coupling. 

Safa, A. R., Roberts, S., Agresti, M., Fine, R. L., Tamoxifen aziridine, a novel affinity probe for P-glycoprotein in multidrug resistant cells, Biochem. Biophys. Res. Commun. 1994, 202, 606-612. 

Cutler, G. B., Fojo, T., Bates, S. E., Steroid treatment, accumulation, and antagonism of P-glycoprotein in multidrug-resistant cells, Biochemistry 1996, 35, 4820-4827. 

Thimmaiah, K.N., Horton, J.K., Qian, X.D., Beck, W.T., Houghton, J.A. and Houghton, J. (1990) Structural determinants of phenoxazine type compounds required to modulate the accumulation of vinblastine and vincristine in multidrug-resistant cell lines. Cancer Communications, 2, 249-259. 

Chemical Synthesis and Biological Studies of the Epothilones - Microtubule Stabilizing Agents with Enhanced Activity Against Multidrug-Resistant Cell Lines and Tumors. 

J. Troost, H. Lindenmaier, W. E. Haefeli, and J. Weiss. Modulation of cellular cholesterol alters P-glycoprotein activity in multidrug-resistant cells. Mol. Pharmacol. 66 1332-1339 (2004). 

Cyclopamine also interferes with cholesterol metabolism that results in decreased cholesterol synthesis and the accumulation of late biosynthetic intermediates. Cyclopamine was evaluated as an inhibitor of multi-drug resistance in tumor cells. Intrinsic or acquired resistance of tumor cells to cytotoxic drugs is a major cause of failure of chemotherapy. Both cyclopamine and the spirosolane alkaloid tomatidine from tomatoes act as potent and elfective chemosensitizers in multidrug-resistant cells (Lavie et ah, 2001). Therefore, plant steroidal alkaloids, such as cyclopamine and tomatidine, or their analogs, may serve as chemosensitizers in combination with chemotherapy and conventional cytotoxic drugs for treating multidrug-resistant cancers. 

Fine et al. described that the activity of PKC was 7-fold higher in multidrug resistant cells compared with the sensitive parental breast cancer cells (Fine et al., 1988). An over 6-fold increase in PKC activity in the MDR human breast cancer subline MCF-7/DOXR was confirmed vdien compared with the sensitive parent cell line, MCF-7AVT (Schwartz et al., 1991). Aquino et al. found that multidrug resistant HL-60/ADR cells contained 2-fold more PKC than the parental cell line (Aquino et al., 1988). In four murine UV-2237M... 

Emanuel SL, Chamberlin HA, Cohen D (1999) Antimitotic drugs cause increased tumorigenidty of multidrug resistant cells. Int J Oncol 14 487-494 Emoto Y, Manome Y, Meinhardt G, Kisaki H, Kharbanda S, Robertson M, Ghayur T, Wong WW, Kamen R, Weichsdbaum R, Kufe D (1995) Proteolytic activation of protein kinase C delta by an ICE like protease in apoptotic cells. EMBO J 14 6148-6156... 

Hu YP, Robert J (1997) Inhibition of protein kinase C in multidrug-resistant cells by modulators of multidrug resistance.) Cancer Res Clin Oncol 123 201-210... 

Regev R, Assaraf YG, Eytan GD (1999) Membrane fluidization by ehter, other anesthetics, and certain agents abolishes P-glycoprotein ATPase activity and modulates efflux from multidrug-resistant cells. Eur J Biochem 259 18-24... 

Sato W, Yusa K, Naito M, Tsuruo T (1990) Staurosporine, a potent inhibitor of C-kinase, enhances drug accumulation in multidrug-resistant cells. Biochem Biophys Res Comm 173 1252-1257... 

Epothilones are naturally occurring cytotoxic macrolides, which were initially isolated from a mycobacterium. Their antitumor activity is similar to that of the clinically established taxoids (Taxol, Taxotere), by interrupting the dynamic mechanism of microtubule assembly/disassembly via microtubule stabilization. In contrast to taxoids, epothilones are remarkably efficient against multidrug resistant cells. 

Altenberg GA, Vanoye CG, Horton JK, et al. Unidirectional fluxes of rhodamine 123 in multidrug-resistant cells evidence against direct drug extrusion from the plasma membrane. Proc Natl Acad Sci USA 1994 91 ( I I ) 4654 4657. 

Tamai I, Safa AR. Azidopine noncompetitively interacts with vinblastine and cyclosporin A binding to P-glycoprotein in multidrug resistant cells. J Biol Chem 1991 266(25) 16796-16800. 

Eytan GD, Regev R, Oren G, et al. Efficiency of P-glycoprotein-mediated exclusion of rhodamine dyes from multidrug-resistant cells is determined by their passive transmembrane movement rate. Eur J Biochem 1997 248(1) 104—112. 

Molinari A, Cianfriglia M, Meschini S, et al. P-glycoprotein expression in the Golgi apparatus of multidrug-resistant cells. Int J Cancer 1994 59(6) 789-795. 

Horio M, Gottesman MM, Pastan I. ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. Proc Natl Acad Sci U S A 1988 85... 

Epothiione B (Figure 25) is a 16-membered lactone to which an oxirane is fused highly cytotoxic with activity against multidrug resistant cell lines, it has been the subject of total syntheses by Danishefsky <1997AGE757>, Nicolaou <1997NAT268>, and Avery <20010L3607>. 

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