Cancer multidrug resistance, modulator

Cabot, M. C., Giulano, A. E., Han, T-Y., and Liu, Y-Y., 1999, SDZ PSC 833, the cyclosporin A analog and multidrug resistance modulator, activates ceramide synthesis and increases vinblastine sensitivity in drug-sensitive and drag-resistant cancer cells. Cancer Res. 59 880-885. 

Lucci, A., Han, T. Y., Liu, Y. Y., Giuliano, A. R, and Cabot, M. C., 1999b, Multidrug resistance modulators and doxorubicin synergize to elevate ceramide levels and elicit apoptosis in drug-resistant cancer cells. Cancer 86 299-310. 

Booth CL, Brouwer KR, Brouwer KL. Effect of multidrug resistance modulators on the hepatobiliary disposition of doxorubicin in the isolated perfused rat liver. Cancer Res 1998 58(16) 3641-3648. 

Wishart GC, Plumb JA, Morrison JG, et al. Adequate tumour quinidine levels for multidrug resistance modulation can be achieved in vivo. Eur J Cancer 1992 28 (1) 28—31. 

Lee EJ, George SL, Caligiuri M, et al. Parallel phase I studies of daunorubicin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myeloid leukemia results of cancer and leukemia group B study 9420. J Clin Oncol 1999 17(9) 2831-2839. 

Propafenone 143, a drug in clinical use as an antiarrhythmic, has activity in the modulation of cancer multidrug resistance. A series of benzofuran analogues of propafenone, such as compound 144, have been synthesized and evaluated in a daunomycin cytotoxicity assay <1996JME4767>. The results of this work were later the subject of a comparative molecular field analysis (3-D quantitative structure-activity relationship (QSAR)) <1998QSA301>. 

Pajeva IK, Wiese M. A comparative molecular field analysis of propafenone-type modulators of cancer multidrug resistance. Quant Struct-Act Rel 1998 17 301-12. 

Baer MR, George SL, Dodge RK. Phase 3 study of the multidrug resistance modulator PS C-83 3 in previously untreated patients 60 years of age and older with acute myeloid leukemia Cancer and Leukemia Group B Study 9720. Blood 2002 100 1224-1232. 

Li X, Chen Y, Li PC (2011) A simple and fast microfluidic approach of same-single-cell analysis (SASCA) for the study of multidrug resistance modulation in cancer cells. Lab Chip 11(7) 1378-1384... 

Propafenone-Type Modulators of Cancer Multidrug Resistance. 

Chearwae, W. et al.. Modulation of the function of the multidrug resistance-linked ATP-binding transporter ABCG2 by the cancer chemopreventive agent curcumin. Mol. Cancer Then, 5, 1995, 2006. 

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. 

Brooks T, Minderman H, O Loughlin KL, Pera P, Ojima 1, Baer MR, Bemacki RJ. (2003) Taxane-based reversal agents modulate drug resistance mediated by P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Mol Cancer Ther 2 1195-1205. 

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... 

Sampson E, Wolff CL, Abraham I (1993) Staurosporine reduces P-glycoprotein expression and modulates multidrug resistance. Cancer Lett 68 7-14... 

The in vitro antitumor activity of curcumin in HPV-associated cells has been established [Roy et al., 2002]. Curcumin modulates the in vitro expression and function of Pgp in multidrug-resistant human KB-V1 cells [Anand et al., 2008 Chearwae et al., 2004] and sensitizes cisplatin-resistant SiHa cells to cisplatin-induced apoptosis [Venkatraman et al., 2005], indicating its ability to reverse MDR in cervical cancer cells. The effect of curcumin in HPV-associated cells was found to involve the down-regulation of viral oncogenes, NF-kB and AP-1 [Anand et al., 2008 Divya and Pillai, 2006],... 

Molnar, J., Gyemant, N., Mucsi, I., Molnar, A., Szabo, M., Kortvelyesi, T., Varga, A., Molnar, P., and Toth, G. 2004. Modulation of multidrug resistance and apoptosis of cancer cells by selected carotenoids. In Vivo 18, 237-244. 

The choice of a cell line to study MDR modulator potency was very important for future potential application in human cancer treatment. PhM (12) that were quite effective in resistant mouse lymphoma cells were only slightly active in drug-resistant human sarcoma cell line MES-SA/Dx5 [198]. The drug-sensitive human sarcoma cell line MES-SA and its multidrug-resistant counterpart MES-SA/Dx5 were applied as a model system for evaluation of MDR modulator activities. Examination performed by the flow cytometric Rhl23 accumulation test demonstrated that the well-known P-gp modulators verapamil (79) and TFP (5) reduced MDR in MES-SA/Dx5 cells. In resistant MES-SA/Dx5 cells, verapamil (79) and TFP (5) restored the drug accumulation pattern which was typical for sensitive cells. However, the effectiveness of PhM (12) was very low. The most active compounds were derivatives with an H atom at position 2 of the phenothiazine ring, followed by Cl-substituted and CF3-substituted compounds. 

Modok S, Mellor HR, Callaghan R. Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer. Curr Opin Pharmacol 2006 6(4) 350-354. 

Wilson WH, Bates SE, Fojo A, et al. Modulation of multidrug resistance by dex-verapamil in EPOCH-refractory lymphomas. J Cancer Res Clin Oncol 1995 121 (suppl 3) R25-R29. 

Advani R, Fisher GA, Lum BL, et al. A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC833), a modulator of multidrug resistance. Clin Cancer Res 2001 7 1221-1229. 

Actinomycin D has been clinically used for the treatment of many cancers and is known to be a DNA intercalator. The structure of actinomycin D is based on a phenoxazine ring bound to two cyclic pentapeptides [33]. The presence of the phenoxazine ring in the structure of actinomycin D suggests that phenoxazine derivatives may possess anticancer activity. Phenoxazine derivatives are known to be effective multidrug resistance (MDR) modulators in cancer cells [34], potent inhibitors of Akt signaling in cells [35], inhibitors of human plasma cholinesterase [36], and photo-chemotherapeutic agents in cancer cells [37]. Recent studies also show that the relatively water-soluble phenox-azines, such as 2-amino-4,4a-dihydro-4a,7-dimethyl-2H-phenoxazine-3-one and 2-aminophenoxazine-3-one, exert antitumor effects on various cancer cells in vitro and in vivo. [38]. We have investigated 24 phenoxazines [23,39] (Fig. 4). 

Krishna R, Mayer LD (2000) Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Fur J Pharm Sci 11 265-283... 

Stein U, Walther W, Shoemaker RH (1996) Modulation of mdrl expression by cytokines in human colon carcinoma cells An approach for reversal of multidrug resistance. British Journal of Cancer 74 1384-1391. 

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