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Resistance to antineoplastic agents is the major obstacle to curative therapy of cancer. Tumor cell lines with acquired resistance to the antineoplastic agent cis-diamminedichloroplatinum(II) overexpressed metallothionein and demonstrated cross-resistance to alkylating agents such as chlorambucil and melphalan. Human carcinoma cells that maintained high(More)
The Cdc25 dual specificity phosphatases have central roles in coordinating cellular signaling processes and cell proliferation, but potent and selective inhibitors are lacking. We experimentally examined the 1990 compound National Cancer Institute Diversity Set and then computationally selected from their 140 000 compound repository 30 quinolinediones of(More)
c-Myc is helix-loop-helix-leucine zipper (HLH-ZIP) oncoprotein that is frequently deregulated in human cancers. In order to bind DNA, regulate target gene expression, and function in a biological context, c-Myc must dimerize with another HLH-ZIP protein, Max. A large number of c-Myc target genes have been identified, and many of the encoded proteins are(More)
Molecular mechanism of cell cycle arrest caused by diallyl trisulfide (DATS), a garlic-derived cancer chemopreventive agent, has been investigated using PC-3 and DU 145 human prostate cancer cells as a model. Treatment of PC-3 and DU 145 cells, but not a normal prostate epithelial cell line (PrEC), with growth suppressive concentrations of DATS caused(More)
A synthetic vitamin K analogue, 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone or compound 5 (Cpd 5), was found previously to be a potent inhibitor of tumor cell growth. We now demonstrate that Cpd 5 arrested cell cycle progression at both G1 and G2-M. Because of the potential arylating activity of Cpd 5, it might inhibit Cdc25 phosphatases, which(More)
Phosphatases of regenerating liver (PRL) constitute a subfamily of the protein tyrosine phosphatases that are implicated in oncogenic and metastatic phenotypes. In this study, we evaluated the role of PRL-1 in cell proliferation and metastatic processes in human lung cancer cells. We stably transfected human A549 lung cancer cells with several short hairpin(More)
The cytotoxicities of a number of antineoplastic agents to oxygenated and hypoxic EMT6 mouse mammary tumor cells in culture were examined. Based on the relative sensitivities of cells under aerobic and hypoxic conditions, drugs were placed into three categories. Drugs that were preferentially toxic to cells under oxygenated conditions were classified as(More)
microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain insights into its potential role in tumorigenesis, we generated miR-21 knockout colon cancer cells through gene targeting. Unbiased microarray analysis combined(More)
Embryonic cells from transgenic mice with targeted disruption of metallothionein I and II genes expressed no detectable metallothionein either constitutively or after treatment with cadmium, in contrast to cultured cells that were wild type or heterozygous for the loss of the metallothionein genes. Metallothionein null cells were most sensitive to the(More)
In inflammatory states, nitric oxide (.NO) may be synthesized from precursor L-arginine via inducible .NO synthase (iNOS) in large amounts for prolonged periods of time. When .NO acts as an effector molecule under these conditions, it may be toxic to cells by inhibition of iron-containing enzymes or initiation of DNA single-strand breaks. In contrast to(More)