Disease relevance of Rhodamine 123

• MALD-MS was also capable of demonstrating the reduced accumulation of the cationic drug rhodamine-123 by DoxR MCF7, a multiply drug-resistant human breast adenocarcinoma cell line, relative to the nonresistant parent line MCF7 [1].
• In this study tumor cell P-170 expression was assessed in 29 patients suffering from acute leukemia (17 acute myeloid leukemia (AML) and 12 acute lymphoblastic leukemia (ALL)) using three different techniques: flow cytometry measuring rhodamine 123 (Rh123) efflux (functional level), immunocytochemistry (protein level) and RT-PCR (mRNA level) [2].
• Hypothyroidism prevents postnatal changes in rat liver mitochondrial populations defined by rhodamine-123 staining [3].
• The effects of Klebsiella pneumoniae endotoxin on the biliary excretion and renal handling of rhodamine-123 were investigated in rats at different times after intraperitoneal injection (1 mg/kg of body weight) [4].
• Fluorescent probes rhodamine 123 (Rh123), bisbenzimide (Bis), and rhodamine 6G (Rh6G) were administered for the identification by intravital fluorescence microscopy (IVFM) of mitochondrial membrane potential, hepatocyte nuclei and leukocytes, respectively before hepatic ischemia and at 15, 30, 45, and 60 min after reperfusion [5].

High impact information on Rhodamine 123

• Rh123 and several other fluorescent dyes are substrates for transport mediated by P-glycoprotein (P-gp), an efflux pump responsible for multidrug resistance in tumor cells [6].
• Rhodamine-123, a cationic laser dye, markedly reduced the clonal growth of carcinoma cells but had little effect on nontumorigenic epithelial cells in vitro [7].
• Finally, we demonstrated that the Endo(Pos) Sca-1(Pos) Rh(Low) (Rhodamine-123 low) phenotype, without using CD34, c-Kit, or Lineage markers, defines a nearly homogenous population of LTR-HSCs [8].
• Both Rh123 fractions proliferated in response to MGF alone as determined by a [3H]TdR assay or by counting nucleated cells present in the cultures over time [9].
• Stimulation of both Rh123 fractions with MGF alone did not result in a net increase of day 14 CFU-S [9].

Chemical compound and disease context of Rhodamine 123

• RESULTS: Treatment of cells with hyperthermia or ultrasound (20 min at 41 degrees C) both caused a significant increase over controls (no ultrasound treatment) in R123 and DOX accumulation in the parent and MDR lines of MV522 and KB cells [10].
• Dequalinium and rhodamine-123, drugs selectively accumulated in malignant cells, were found to be potent calmodulin antagonists, and inhibited the growth of C6 astrocytoma cells [11].
• We assessed the effects of combining ultrasound-induced hyperthermia (USHT) with the P-glycoprotein modulator PSC 833 on cellular retention and cytotoxicity of rhodamine 123 (R123) and doxorubicin in the parent and multidrug resistance (MDR) variants of two human cancer lines [12].
• Here we evaluate the phototoxic properties of four bromine derivatives of rhodamine-123 toward human uterine sarcoma (MES-SA) and green monkey kidney (CV-1) cells and compare the degrees of tumor cell selectivity associated with these dyes with those associated with two model mitochondrial triarylmethanes (crystal violet and ethyl violet) [13].
• A resistant cell line and cells from 11 patients with chronic lymphoid leukemia B were used for the evaluation of intracellular accumulation of daunorubicin (DNR), idarubicin (IDA), epirubicin (EPI) and rhodamine-123 (Rh-123) [14].

Biological context of Rhodamine 123

• In contrast, Rh123-dull cells proliferated only in the presence of interleukin 3 and SCF, but total cell numbers rose to a peak of 18,000 by day 21, and one-third of the cells were CFC [15].
• ST used at subtoxic concentrations induced a twofold to threefold enhancement of DNR cytotoxicity, increased Rh123 accumulation, and decreased Rh123 efflux kinetics in resistant AML cells [16].
• Furthermore, an increase of rhodamine-123 uptake into intact cells, which has been explained by mitochondrial swelling, occurred considerably later than the caspase activation and was blocked by Z-VAD-fmk [17].
• On the basis of PCR and rhodamine-123 efflux data, up to 18% +/- 4% of transduced cells were calculated to express the transgene [18].
• Low-intensity fluorescence of rhodamine-123 (Rh-123) discriminates a quiescent hematopoietic stem cell (HSC) population in mouse bone marrow, which provides stable, long-term hematopoiesis after transplantation [19].

Anatomical context of Rhodamine 123

• When compared for ability to inhibit growth of human marrow in soft agar, 10 microM gossypol shows little effect on colony formation whereas 10 microM rhodamine-123 completely prevents stem cell growth, suggesting that gossypol may have the most favorable therapeutic index [20].
• Benzo(a)pyrene did not accumulate in acidic compartments, based on acridine orange fluorescence, or in mitochondria, based on rhodamine-123 fluorescence [21].
• Initially, the Rh123-bright and Rh123-dull cells had few CFC but, in the presence of interleukin 3 and SCF, Rh123-bright cells gave rise to greater than 15,000 granulocyte/macrophage CFC, greater than 1500 erythroid burst-forming cells, and greater than 700 mixed-cell CFC by day 5 [15].
• Furthermore, activation of PKCdelta in keratinocytes altered mitochondrial membrane potential, as indicated by rhodamine-123 fluorescence [22].
• Release of IL-2 was significantly suppressed by these inhibitors at concentrations that were also effective in blocking efflux of Rhodamine-123 from normal T lymphocytes [23].

Associations of Rhodamine 123 with other chemical compounds

• Normal or day-6 post-5-fluorouracil light-density bone marrow (BM) was sorted on the basis of differences in rhodamine-123 (Rh123) retention or wheat germ agglutinin (WGA) affinity and tested in vivo using a recently developed alpha-thalassemic chimeric mouse model [24].
• Activation of adult HSCs in vivo following 5-fluorouracil treatment, or in vitro with cytokines, induces variable losses in Rhodamine-123 and Hoechst 33342 efflux activities, and HSCs from mdr-1a/1b(-/-) mice show a dramatic decrease in Rhodamine-123 efflux ability [25].
• This included an analysis of the light scattering properties of these progenitors, as well as their expression of CD34 and HLA-DR, Rhodamine-123 staining, and in vitro sensitivity to 4-hydroperoxycyclophosphamide [26].
• Accumulation of the P-glycoprotein substrate rhodamine-123 was measured by flow cytometry, with and without the cyclosporin D analogue SDZ PSC 833 [27].
• The transportal infusion of lipopolysaccharide also decreased rhodamine-123 fluorescence in perfused rat liver [28].

Gene context of Rhodamine 123

• Flow cytometric analysis of MDR1 expression (D) and function (rhodamine-123 efflux) was obtained in 203 and 158 patients, respectively [29].
• In a nonhematological model, the P-gp expressing HCT-8 adenocarcinoma cell line, exogenously added IL-2 was shown to exert an inhibitory effect on P-gp mediated Rhodamine-123 efflux [23].
• In contrast to R123, a 60 min DNR or calcein-AM accumulation test could be used to detect MRP-mediated resistance [30].
• MATERIALS AND METHODS: Extremely primitive Bcr-Abl fusion positive cells were purified from patients with CML using multiparameter flow cytometric analysis of CD34, Thy, and lineage marker (Lin) expression, plus rhodamine-123 (Rh-123) brightness [31].
• Uptake studies in the presence and absence of rhodamine 123 (R123; 3.2 and 5.0 microM) were also performed in a Pgp overexpressing cell line, MCF-7/Adr [32].

Analytical, diagnostic and therapeutic context of Rhodamine 123

• Rhodamine 123 (Rh123) staining and flow cytometry analysis showed a significantly decreased mean fluorescence in 51 C219+ and 38 JSB1+ patients compared to 42 MDR negative ones (P < .001) [33].
• The techniques discussed include classic imaging techniques, such as rhodamine-123, the highly advanced semi-conductor nanoparticles (quantum dots), and wide field microscopy as well as high-resolution multiphoton imaging [34].
• Immunofluorescence experiments suggest that T cells from old and young mice have equal amounts of the P-Gp molecule itself, suggesting that differences in R123 extrusion may depend on posttranslational regulation of P-Gp activity [35].
• After direct microinjection of R123 into the vacuole in which the parasite grows and multiples, the dye appeared in the host-cell mitochondria but not in the parasite's mitochondria [36].
• A low Rh123 accumulation and a high Rh123 efflux blocking by PSC833 were associated with a low complete remission (CR) rate after the first cycle of chemotherapy (P = 0.008 and P = 0.01, respectively) [37].

References