scholarly journals Single-cell mapping of DNA G-quadruplex structures in human cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Winnie W. I. Hui ◽  
Angela Simeone ◽  
Katherine G. Zyner ◽  
David Tannahill ◽  
Shankar Balasubramanian
Keyword(s):  
Secondary Structure ◽  
Single Cell ◽  
Genome Instability ◽  
Human Cancer ◽  
Single Cells ◽  
Dna Secondary Structure ◽  
Genomic Locus ◽  
Mixed Cell ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells

AbstractG-quadruplexes (G4s) are four-stranded DNA secondary structures that form in guanine-rich regions of the genome. G4s have important roles in transcription and replication and have been implicated in genome instability and cancer. Thus far most work has profiled the G4 landscape in an ensemble of cell populations, therefore it is critical to explore the structure–function relationship of G4s in individual cells to enable detailed mechanistic insights into G4 function. With standard ChIP-seq methods it has not been possible to determine if G4 formation at a given genomic locus is variable between individual cells across a population. For the first time, we demonstrate the mapping of a DNA secondary structure at single-cell resolution. We have adapted single-nuclei (sn) CUT&Tag to allow the detection of G4s in single cells of human cancer cell lines. With snG4-CUT&Tag, we can distinguish cellular identity from a mixed cell-type population solely based on G4 features within individual cells. Our methodology now enables genomic investigations on cell-to-cell variation of a DNA secondary structure that were previously not possible.

scholarly journals Monohydrazone Based G-Quadruplex Selective Ligands Induce DNA Damage and Genome Instability in Human Cancer Cells

2020 ◽  
Vol 63 (6) ◽  
pp. 3090-3103 ◽  
Author(s):  
Jussara Amato ◽  
Giulia Miglietta ◽  
Rita Morigi ◽  
Nunzia Iaccarino ◽  
Alessandra Locatelli ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cancer Cells ◽  
Genome Instability ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
G Quadruplex ◽  
Selective Ligands

Bioguided Identification of Antifungal and Antiproliferative Compounds from the Brazilian Orchid Miltonia flavescens Lindl.

2014 ◽  
Vol 69 (1-2) ◽  
pp. 46-52 ◽  
Author(s):  
Leticia F. Porte ◽  
Silvana M. O. Santin ◽  
Lucas U. R. Chiavelli ◽  
Cleuza C. Silva ◽  
Terezinha J. Faria ◽  
...  
Keyword(s):  
Human Cancer ◽  
Antifungal Compound ◽  
Chloroform Fraction ◽  
Human Cancer Cell ◽  
Human Ovary ◽  
Therapeutic Application ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Cladosporium Herbarum ◽  
Hydrocinnamic Acid

The Orchidaceae family is appreciated worldwide for the beauty of its flowers, and hundreds of species of this family occur in Brazil. Yet little is known about the potential of orchids for therapeutic application. We have investigated bioactive compounds produced by the South Brazilian orchid Miltonia flavescens Lindl. Bioguided studies with the fungus Cladosporium herbarum allowed the identification of hydrocinnamic acid as the active antifungal compound. In addition, the chloroform fraction exhibited an interesting activity against human cancer cells, and 5,7-dihydroxy-6,4'- dimethoxyflavone isolated from this fraction was found to be active against seven human cancer cell lines, including NCI/ADR-RES ovary sarcoma, with an IC50 value of 2.6 mg/mL. This is the first report on the cytostatic activity of this flavone against human ovary sarcoma.

scholarly journals Selective vulnerability of aneuploid human cancer cells to inhibition of the spindle assembly checkpoint

2020 ◽  
Author(s):  
Yael Cohen-Sharir ◽  
James M. McFarland ◽  
Mai Abdusamad ◽  
Carolyn Marquis ◽  
Helen Tang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cellular Response ◽  
Large Scale ◽  
Spindle Assembly Checkpoint ◽  
Human Cancer ◽  
Spindle Assembly ◽  
Selective Vulnerability ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Diploid Cells

AbstractSelective targeting of aneuploid cells is an attractive strategy for cancer treatment. Here, we mapped the aneuploidy landscapes of ~1,000 human cancer cell lines and classified them by their degree of aneuploidy. Next, we performed a comprehensive analysis of large-scale genetic and chemical perturbation screens, in order to compare the cellular vulnerabilities between near-diploid and highly-aneuploid cancer cells. We identified and validated an increased sensitivity of aneuploid cancer cells to genetic perturbation of core components of the spindle assembly checkpoint (SAC), which ensures the proper segregation of chromosomes during mitosis. Surprisingly, we also found highly-aneuploid cancer cells to be less sensitive to short-term exposures to multiple inhibitors of the SAC regulator TTK. To resolve this paradox and to uncover its mechanistic basis, we established isogenic systems of near-diploid cells and their aneuploid derivatives. Using both genetic and chemical inhibition of BUB1B, MAD2 and TTK, we found that the cellular response to SAC inhibition depended on the duration of the assay, as aneuploid cancer cells became increasingly more sensitive to SAC inhibition over time. The increased ability of aneuploid cells to slip from mitotic arrest and to keep dividing in the presence of SAC inhibition was coupled to aberrant spindle geometry and dynamics. This resulted in a higher prevalence of mitotic defects, such as multipolar spindles, micronuclei formation and failed cytokinesis. Therefore, although aneuploid cancer cells can overcome SAC inhibition more readily than diploid cells, the proliferation of the resultant aberrant cells is jeopardized. At the molecular level, analysis of spindle proteins identified a specific mitotic kinesin, KIF18A, whose levels were drastically reduced in aneuploid cancer cells. Aneuploid cancer cells were particularly vulnerable to KIF18A depletion, and KIF18A overexpression restored the sensitivity of aneuploid cancer cells to SAC inhibition. In summary, we identified an increased vulnerability of aneuploid cancer cells to SAC inhibition and explored its cellular and molecular underpinnings. Our results reveal a novel synthetic lethal interaction between aneuploidy and the SAC, which may have direct therapeutic relevance for the clinical application of SAC inhibitors.

scholarly journals System-Wide Analysis of Protein Acetylation and Ubiquitination Reveals a Diversified Regulation in Human Cancer Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 411 ◽  
Author(s):  
Hiroko Kozuka-Hata ◽  
Aya Kitamura ◽  
Tomoko Hiroki ◽  
Aiko Aizawa ◽  
Kouhei Tsumoto ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Translational Control ◽  
Large Scale ◽  
Human Cancer ◽  
Initiation Factor ◽  
Protein Acetylation ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Lysine Modification

Post-translational modifications are known to be widely involved in the regulation of various biological processes, through the extensive diversification of each protein function at the cellular network level. In order to unveil the system-wide function of the protein lysine modification in cancer cell signaling, we performed global acetylation and ubiquitination proteome analyses of human cancer cells, based on high-resolution nanoflow liquid chromatography–tandem mass spectrometry, in combination with the efficient biochemical enrichment of target modified peptides. Our large-scale proteomic analysis enabled us to identify more than 5000 kinds of ubiquitinated sites and 1600 kinds of acetylated sites, from representative human cancer cell lines, leading to the identification of approximately 900 novel lysine modification sites in total. Very interestingly, 236 lysine residues derived from 141 proteins were found to be modified with both ubiquitination and acetylation. As a consequence of the subsequent motif extraction analyses, glutamic acid (E) was found to be highly enriched at the position (−1) for the lysine acetylation sites, whereas the same amino acid was relatively dispersed along the neighboring residues of the lysine ubiquitination sites. Our pathway analysis also indicated that the protein translational control pathways, such as the eukaryotic initiation factor 2 (EIF2) and the ubiquitin signaling pathways, were highly enriched in both of the acetylation and ubiquitination proteome data at the network level. This report provides the first integrative description of the protein acetylation and ubiquitination-oriented systematic regulation in human cancer cells.

Sesquiterpene lactones from Carpesium rosulatum with potential cytotoxicity against five human cancer cell lines

2010 ◽  
Vol 30 (8) ◽  
pp. 1083-1087 ◽  
Author(s):  
Hyung-In Moon ◽  
Okpyo Zee
Keyword(s):  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Sesquiterpene Lactone ◽  
Cell Lines ◽  
Human Cancer ◽  
Sesquiterpene Lactones ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Whole Plant

In search for plant-derived cytotoxicity compound against human cancer cells (A549, SK-OV-3, SK-MEL-2, XF498, HCT15), it was found that the chloroform extracts obtained from the whole plant of Carpesium rosulatum MlQ. (Compositae) exhibited significant cytotoxic activity. Four sesquiterpene lactone, CRC1 (2α, 5-epoxy-5,10-dihydroxy-6-angeloyl-oxy-9β-isobutyloxy-germacran-8α,12-olide), CRC2 (2α,5-epoxy-5,10-dihydroxy-6α,9β-diangeloyloxy-germacran-8α,12-olide), CRC3 (2α,5-epoxy-5,10-dihydroxy-6α-angeloyloxy-9β-(3-methyl-butanoyloxy)-gemacran-8α,12-olide), CRC4 (2β,5-epoxy-5,10-dihydroxy-6α,9β-diangeloyloxy-germacran-8α,12-olide) were isolated from the whole parts of C. rosulatum. 2α,5-epoxy-5,10-dihydroxy-6α,9β-diangeloyloxy-germacran-8α,12-olide (CRC2) showed the most potent cytotoxicity with IC50 value of 6.01 μM against SK-MEL-2.

Abstract 4838: R loop-driven genome instability by G-quadruplex binders in BRCA2-silenced human cancer cells

2018 ◽  
Author(s):  
Alessio De Magis ◽  
Stefano Giustino Manzo ◽  
Marco Russo ◽  
Olivier Sordet ◽  
Rita Morigi ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Genome Instability ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
G Quadruplex

Three New Cytotoxic Monoterpenoid Bisindole Alkaloids from Tabernaemontana bufalina

Planta Medica ◽  
2018 ◽  
Vol 84 (15) ◽  
pp. 1127-1133 ◽  
Author(s):  
Si-Yuan Zhou ◽  
Ting-Lan Zhou ◽  
Guofu Qiu ◽  
Xiajuan Huan ◽  
Ze-Hong Miao ◽  
...  
Keyword(s):  
Human Cancer ◽  
Spectroscopic Methods ◽  
Human Cancer Cell ◽  
Inhibitory Effects ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
Aerial Parts ◽  
Ic50 Values ◽  
Circular Dichroic ◽  
Mcf 7

AbstractThree new bisindole alkaloids, 3′-(2-oxopropyl)-19,20-dihydrotabernamine (1), 3′-(2-oxopropyl)-ervahanine B (2), 19,20-dihydrovobparicine (3), and 20 known compounds were isolated from the aerial parts of Tabernaemontana bufalina. The structures of these alkaloids were elucidated using spectroscopic methods. The absolute configurations of 1–3 were determined by the circular dichroic exciton chirality method. Compounds 1–23 were screened for their cytotoxicity against two human cancer cell lines, A-549 and MCF-7. Ten compounds (1–3, 10, 14, 16, 17, 19, 22, and 23) exhibited inhibitory effects against the two human cancer cells with IC50 values of 1.19 ~ 6.13 µM.

scholarly journals Holliday junction trap shows how cells use recombination and a junction-guardian role of RecQ helicase

2016 ◽  
Vol 2 (11) ◽  
pp. e1601605 ◽  
Author(s):  
Jun Xia ◽  
Li-Tzu Chen ◽  
Qian Mei ◽  
Chien-Hui Ma ◽  
Jennifer A. Halliday ◽  
...  
Keyword(s):  
Dna Damage ◽  
Genome Instability ◽  
Human Cancer ◽  
Single Cells ◽  
Strand Break ◽  
Holliday Junctions ◽  
Dna Breaks ◽  
E Coli ◽  
Dna Replication And Repair ◽  
The Many

DNA repair by homologous recombination (HR) underpins cell survival and fuels genome instability, cancer, and evolution. However, the main kinds and sources of DNA damage repaired by HR in somatic cells and the roles of important HR proteins remain elusive. We present engineered proteins that trap, map, and quantify Holliday junctions (HJs), a central DNA intermediate in HR, based on catalytically deficient mutant RuvC protein ofEscherichia coli. We use RuvCDefGFP (RDG) to map genomic footprints of HR at defined DNA breaks inE. coliand demonstrate genome-scale directionality of double-strand break (DSB) repair along the chromosome. Unexpectedly, most spontaneous HR-HJ foci are instigated, not by DSBs, but rather by single-stranded DNA damage generated by replication. We show that RecQ, theE. coliortholog of five human cancer proteins, nonredundantly promotes HR-HJ formation in single cells and, in a novel junction-guardian role, also prevents apparent non-HR–HJs promoted by RecA overproduction. We propose that one or more human RecQ orthologs may act similarly in human cancers overexpressing the RecA orthologRAD51and find that cancer genome expression data implicate the orthologs BLM and RECQL4 in conjunction with EME1 and GEN1 as probable HJ reducers in such cancers. Our results support RecA-overproducingE. colias a model of the many human tumors with up-regulatedRAD51and provide the first glimpses of important, previously elusive reaction intermediates in DNA replication and repair in single living cells.

scholarly journals Compounds with Antiproliferative Activity on Five Human Cancer Cell Lines from South Korean Carpesium triste

2012 ◽  
Vol 7 (7) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Hyung-In Moon
Keyword(s):  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Sesquiterpene Lactones ◽  
Human Cancer Cell ◽  
Human Cancer Cell Lines ◽  
Human Cancer Cells ◽  
South Korean ◽  
Whole Plant

In the search for antiproliferative compounds against human cancer cells (A549, SK-OV-3, SK-MEL-2, XF498, HCT15), it was found that the chloroform extracts obtained from the whole plant of Carpesium rosulatum Miq. (Compositae) exhibited significant cytotoxic activity. Two sesquiterpene lactones, CT-1 (2α,5-epoxy-5,10-dihydroxy-6-angeloyloxy-9β-isobutyloxy-germacran-8α,12-olide), and CT-2 (2β,5-epoxy-5,10-dihydroxy-6α,9β-diangeloyloxy-germacran-8α,12-olide) were isolated from the whole plant. CT-2 showed the most potent cytotoxicity with an IC50 value of 7.88 μM against SK-MEL-2.

scholarly journals SMOOTH-seq: single-cell genome sequencing of human cells on a third-generation sequencing platform

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xiaoying Fan ◽  
Cheng Yang ◽  
Wen Li ◽  
Xiuzhen Bai ◽  
Xin Zhou ◽  
...  
Keyword(s):  
Single Cell ◽  
Genome Sequencing ◽  
Single Molecule ◽  
Human Cancer ◽  
Whole Genome ◽  
Third Generation ◽  
Sequencing Platform ◽  
Human Cancer Cell Lines ◽  
Third Generation Sequencing ◽  
Generation Sequencing

AbstractThere is no effective way to detect structure variations (SVs) and extra-chromosomal circular DNAs (ecDNAs) at single-cell whole-genome level. Here, we develop a novel third-generation sequencing platform-based single-cell whole-genome sequencing (scWGS) method named SMOOTH-seq (single-molecule real-time sequencing of long fragments amplified through transposon insertion). We evaluate the method for detecting CNVs, SVs, and SNVs in human cancer cell lines and a colorectal cancer sample and show that SMOOTH-seq reliably and effectively detects SVs and ecDNAs in individual cells, but shows relatively limited accuracy in detection of CNVs and SNVs. SMOOTH-seq opens a new chapter in scWGS as it generates high fidelity reads of kilobases long.

Sign in / Sign up

Export Citation Format

Share Document