Mouse leukemia cells derivatives

In 1997, Chakrabarty et al. reported the isolation of 9-carbethoxy-3-methylcarba-zole (5) and 9-formyl-3-methylcarbazole (6) from the roots of M. koenigii (17). These metabolites are the first 9-formyl and 9-carbethoxy carbazole derivatives obtained from plant sources. 9-Formyl-3-methylcarbazole (6) showed weak cytotoxicity against both mouse melanoma B16 and adriamycin-resistant P388 mouse leukemia cell lines. The structural assignment of these two alkaloids was based on the IR- and H-NMR spectra which were lacking any signal of an NH group. Additional structural support for 9-carbethoxy-3-methylcarbazole (5) was provided by the similarity of the UV absorption spectrum with that of a synthetic sample, obtained by reaction of 3-methylcarbazole with ethyl chloroformate in the presence of base. Further structural support for 9-formyl-3-methylcarbazole (6) was derived from a comparison of the UV spectrum and the IR carbonyl absorption (1696 cm ) with those of an authentic sample of 9-formyl-3-methylcarbazole (1700 cm ), prepared by the treatment of 3-methylcarbazole (2) with 98% formic acid (17) (Scheme 2.3). 

At nanomolar to micromolar concentrations, yessotoxin has been shown to be toxic to many mammalian cells in culture, including a BE(2)-M17 neuroblastoma cell line [37], a human neuroblastoma cell line [38], HeLa S3 cells [39], rat L6 and mouse BC3H1 skeletal muscle myoblast cell lines [40], P388 mouse leukemia cells [41], 3T3 mouse fibroblasts [42], rat hepatocytes [43], and isolated cerebellar neurons [44]. Yessotoxin did not cause significant mortality in MCE breast cancer cells at nanomolar concentrations, although growth was inhibited [45]. Toxicity to an insect cell line (IPLB-LdFB), derived from a lepidopteran larval fat body, has also been demonstrated [42]. 

The activity of 1-P-D-arablnofuranosyl cytidlne (ara-C or CA) against leukemia in man led Wechter O to synthesize various nucleotides of CA and dlnucleoslde phosphates of the type CApX and XpCA where X represents a second nucleoside. The simple nucleotides were cytotoxic di-nucleoslde phosphates with a 3 ->5 linkage were more active than those of 2 — 5 configuration, Mouse leukemia cells resistant to ara-C were also resistant to its phosphorylated derivatives. 

Wang JC, Dick JE. Cancer stem cells lessons from leukemia. Trends Cell Biol 2005 15 494-501. Becker AJ, McCulloch CE, Till JE. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963 197 452 54. 

The title substituted 6 phenylpurine bases and nucleosides 10—13, as well as some acetyl derivatives 8, were tested on their in vitro inhibition of the cell growth in the following cell cultures mouse leukemia L1210 cells (ATCC CCL 219) murine L929 cells (ATCC CCL 1) human cervix carcinoma HeLa S3 cells (ATCC CCL 2.2) and human T lymphoblastoid CCRF-CEM cell line (ATCC CCL 119). Only substituted 6-phenylpurine ribonucleosides 12 and their triacetates 8 exhibited significant activity in these assays (Table 1), while the bases 10 and 11, as well as the 2 amino 6 phenylpurine ribonucleosides 13, were entirely inactive. 

The second cannabinoid receptor sub-type, CB2, was derived from a human promyelocytic leukemia cell HL60 cDNA library (Munro et al. 1993). The human CB2 receptor exhibits 68% identity to the human CBi receptor within the transmembrane regions, 44% identity throughout the whole protein. The CB2 receptor in both rat (Griffin et al. 2000) and mouse (Shire et al. 1996) has been cloned as well. A helix net representation of the human CB2 receptor sequence is presented in Fig. 2. Unlike the CB 1 receptor, which is highly conserved across human, rat, and... 

The conclusion that cathepsin D and the other lysosomal enzymes reside together in the same cell is supported by recent findings with mouse leukemia L1210 cells (8). These cells, which presumably represent a homogeneous, clonally-derived population of lymphocytes, also possess normal lysosomes, as well as cathepsin D which occurs mostly in an unsedimentable form after fractionation. 

---