Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of platinum(II) complexes bearing Delta (4)-1,2,4-oxadiazoline ligands have been synthesized and characterized. Their in vitro antitumor activity has been assessed in platinum-sensitive and -resistant human ovarian cancer cell lines (PEO1, PEOCisR, PEOCarboR, and SK-OV3), as well as in colon cancer (SW948) and testicular cancer cell lines (N-TERA). All compounds tested showed potent cytotoxicity in the platinum-sensitive cell lines and retained activity in the cisplatin- and carboplatin-resistant lines, with IC 50 values similar to the parental drug sensitive counterpart. We propose, therefore, that platinum(II) oxadiazoline complexes may possess a novel mechanism of action, which render them active in tumor cells, with resistance to currently used platinum anticancer agents.
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PMID:Synthesis and characterization of platinum(II) oxadiazoline complexes and their in vitro antitumor activity in platinum-sensitive and -resistant cancer cell lines. 1807 19

Topoisomerase I-DNA-cleavage complexes (Top1cc) stabilized by camptothecin (CPT) have specific effects at transcriptional levels. We recently reported that Top1cc increase antisense transcript (aRNAs) levels at divergent CpG-island promoters and, transiently, DNA/RNA hybrids (R-loop) in nuclear and mitochondrial genomes of colon cancer HCT116 cells. However, the relationship between R-loops and aRNAs was not established. Here, we show that aRNAs can form R-loops in N-TERA-2 cells under physiological conditions, and that promoter-associated R-loops are somewhat increased and extended in length immediately upon cell exposure to CPT. In contrast, persistent Top1ccs reduce the majority of R-loops suggesting that CPT-accumulated aRNAs are not commonly involved in R-loops. The enhancement of aRNAs by Top1ccs is present both in human colon cancer HCT116 cells and WI38 fibroblasts suggesting a common response of cancer and normal cells. Although Top1ccs lead to DSB and DDR kinases activation, we do not detect a dependence of aRNA accumulation on ATM or DNA-PK activation. However, we showed that the cell response to persistent Top1ccs can involve an impairment of aRNA turnover rather than a higher synthesis rate. Finally, a genome-wide analysis shows that persistent Top1ccs also determine an accumulation of sense transcripts at 5'-end gene regions suggesting an increased occurrence of truncated transcripts. Taken together, the results indicate that Top1 may regulate transcription initiation by modulating RNA polymerase-generated negative supercoils, which can in turn favor R-loop formation at promoters, and that transcript accumulation at TSS is a response to persistent transcriptional stress by Top1 poisoning.
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PMID:Dynamic Effects of Topoisomerase I Inhibition on R-Loops and Short Transcripts at Active Promoters. 2678 95