scholarly journals A human cancer cell line initiates DNA replication normally in the absence of ORC5 and ORC2 proteins

2020 ◽  
Vol 295 (50) ◽  
pp. 16949-16959
Author(s):  
Etsuko Shibata ◽  
Anindya Dutta
Keyword(s):  
Dna Replication ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Origin Recognition Complex ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Aaa Atpase ◽  
Normal Number ◽  
Mutant Cells

The origin recognition complex (ORC), composed of six subunits, ORC1–6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2–7, the minichromosome maintenance protein complex, around DNA and initiate DNA replication. We previously reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a reduction in the number of origins firing. Here, using CRISPR-Cas9–mediated mutations, we report that human HCT116 colon cancer cells also survive when ORC5 protein expression is abolished via a mutation in the initiator ATG of the ORC5 gene. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2–7 and initiate replication from a similar number of origins as WT cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells, rendering both ORC5 and ORC2 proteins undetectable in the same cells and destabilizing the ORC1, ORC3, and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2–7 normally to chromatin, and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2–7 to initiate DNA replication, or human cell lines can sometimes recruit MCM2–7 to origins independent of ORC.

scholarly journals A human cancer cell line initiates DNA replication normally in the absence of ORC5 and ORC2 proteins

2020 ◽  
Author(s):  
Etsuko Shibata ◽  
Anindya Dutta
Keyword(s):  
Dna Replication ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Origin Recognition Complex ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Aaa Atpase ◽  
Normal Number ◽  
Mutant Cells

ABSTRACTThe Origin Recognition Complex (ORC), composed of six subunits, ORC1-6, binds to origins of replication as a ring-shaped heterohexameric ATPase that is believed to be essential to recruit and load MCM2-7 around DNA and initiate DNA replication. We had reported the creation of viable cancer cell lines that lacked detectable ORC1 or ORC2 protein without a significant decrease in the number of origins firing. We now report that human HCT116 colon cancer cells also survive with a mutation in the initiator ATG of the ORC5 gene that abolishes the expression of ORC5 protein. Even if an internal methionine is used to produce an undetectable, N terminally deleted ORC5, the protein would lack 80% of the AAA+ ATPase domain, including the Walker A motif. The ORC5-depleted cells show normal chromatin binding of MCM2-7 and initiate replication from similar number of origins as wild type cells. In addition, we introduced a second mutation in ORC2 in the ORC5 mutant cells rendering both ORC5 and ORC2 proteins undetectable in the same cells, and destabilizing the ORC1, ORC3 and ORC4 proteins. Yet the double mutant cells grow, recruit MCM2-7 normally to chromatin and initiate DNA replication with normal number of origins. Thus, in these selected cancer cells, either a crippled ORC lacking ORC2 and ORC5 and present at minimal levels on the chromatin can recruit and load enough MCM2-7 to initiate DNA replication, or human cell-lines can sometimes recruit MCM2-7 to origins independent of ORC.

scholarly journals Secretoglobin 3A2 eliminates human cancer cells through pyroptosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shigetoshi Yokoyama ◽  
Shun Nakayama ◽  
Lei Xu ◽  
Aprile L. Pilon ◽  
Shioko Kimura
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Human Cancer Cells

AbstractNon-canonical inflammasome activation that recognizes intracellular lipopolysaccharide (LPS) causes pyroptosis, the inflammatory death of innate immune cells. The role of pyroptosis in innate immune cells is to rapidly eliminate pathogen-infected cells and limit the replication niche in the host body. Whether this rapid cell elimination process of pyroptosis plays a role in elimination of cancer cells is largely unknown. Our earlier study demonstrated that a multi-functional secreted protein, secretoglobin (SCGB) 3A2, chaperones LPS to cytosol, and activates caspase-11 and the non-canonical inflammasome pathway, leading to pyroptosis. Here we show that SCGB3A2 exhibits marked anti-cancer activity against 5 out of 11 of human non-small cell lung cancer cell lines in mouse xenographs, while no effect was observed in 6 of 6 small cell lung cancer cell lines examined. All SCGB3A2-LPS-sensitive cells express syndecan 1 (SDC1), a SCGB3A2 cell surface receptor, and caspase-4 (CASP4), a critical component of the non-canonical inflammasome pathway. Two epithelial-derived colon cancer cell lines expressing SDC1 and CASP4 were also susceptible to SCGB3A2-LPS treatment. TCGA analysis revealed that lung adenocarcinoma patients with higher SCGB3A2 mRNA levels exhibited better survival. These data suggest that SCGB3A2 uses the machinery of pyroptosis for the elimination of human cancer cells via the non-canonical inflammasome pathway, and that SCGB3A2 may serve as a novel therapeutic to treat cancer, perhaps in combination with immuno and/or targeted therapies.

scholarly journals Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2530
Author(s):  
Ihsan A. Shehadi ◽  
Fatima-Azzahra Delmani ◽  
Areej M. Jaber ◽  
Hana Hammad ◽  
Murad A. AlDamen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Direct Methods ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Colorectal Cancer Cell Line ◽  
Breast Cancer Cell Lines ◽  
Human Cancer Cell Lines

Four new complexes derived from adamantly containing hydrazone (APH) ligand with Cu(II) (1), Co(II) (2), Ni(II) (3) and Zn(II) (4), have been synthesized and characterized using different physicochemical methods. The structure of the ligand APH and its copper complex 1 have been established by single-crystal X-ray diffraction direct methods, which reveal that complex 1 has distorted square-pyramidal geometry. Complexes 1–4 are screened against seven human cancer cell lines namely, breast cancer cell lines (MCF7, T47D, MDA-MB-231), prostate cancer cell lines (PC3, DU145) and the colorectal cancer cell line Coco-2, for their antiproliferative activities. Complex 1 has shown a promising anticancer activity compared to the other ones. The structural and spectroscopic analysis of APH and its complexes are confirmed by DFT calculations.

scholarly journals Triterpenoidal and Phenolic Compounds Isolated from the Aerial Parts of Helicteres hirsuta and their Cytotoxicity on Several Cancer Cell Lines

2019 ◽  
Vol 14 (1) ◽  
pp. 1934578X1901400
Author(s):  
Triet Thanh Nguyen ◽  
Nadine Kretschmer ◽  
Eva-Maria Pferschy-Wenzig ◽  
Olaf Kunert ◽  
Rudolf Bauer
Keyword(s):  
Phenolic Compounds ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Moderate Activity ◽  
Human Cancer Cell Lines ◽  
Aerial Parts ◽  
Helicteres Isora

Helicteres L. is one of the genera of the Sterculiaceae family with several remarkable activities. Previous studies revealed that terpenoids, flavonoids, and lignans are the dominant constituents of Helicteres species. However, information about this genus is scarce and unsystematic. Most of the phytochemical and pharmacological investigations have been mainly reported on Helicteres angustifolia and Helicteres isora, which are commonly used in China and Indonesia, respectively. In the present study, two terpenoids: 3β- O-acetylbetulinic acid (1) and simiarenol (2) together with three phenolic compounds: 4,4'-sulfinylbis(2-( tert-butyl)-5-methylphenol) (3), 7- O-methylisoscutellarein (4), 7,4'-di- O-methylisoscutellarein (5), and a mixture of stigmasterol and β-sitosterol were isolated and structurally elucidated from the aerial parts of Helicteres hirsuta Lour. Compounds 1-5 were tested for cytotoxicity on four human cancer cell lines: leukemia CCRF-CEM, breast MDA-MB-231, colon HCT116 and glioblastoma U251 cancer cells. Among them, compounds 1 and 3 showed moderate activity on CCRF-CEM and HCT116 cancer cells with IC50 values ranging from 14.6 to 31.5 μM (P < 0.05). This is the first time these compounds have been reported from this plant. To the best of our knowledge, compound 3 is novel in nature although it has been chemically synthesized before, and compounds 1, 2, and 4 are new to this plant family (Sterculiaceae).

An IMDAF approach to annellated 1,4:5,8-diepoxynaphthalenes and their metathesis reaction leading to novel scaffolds displaying an antiproliferative activity toward cancer cells

2021 ◽  
Author(s):  
Elizaveta A. Kvyatkovskaya ◽  
Kseniya K. Borisova ◽  
Polina P. Epifanova ◽  
Aleksey A. Senin ◽  
Victor N. Khrustalev ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antiproliferative Activity ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Metathesis Reaction ◽  
Human Cancer Cell Lines ◽  
Antiproliferative Agent

A 3,5a-epoxyfuro[2,3,4-de]isoquinoline scaffold, the product of ROCM of 1,4:5,8-diepoxynaphthalenes, is a promising antiproliferative agent toward breast and prostate human cancer cell lines.

scholarly journals 8-Hydroxycudraxanthone G Suppresses IL-8 Production in SP-C1 Tongue Cancer Cells

2014 ◽  
Vol 9 (1) ◽  
pp. 1934578X1400900
Author(s):  
Arlette S. Setiawan ◽  
Roosje R. Oewen ◽  
Supriatno ◽  
Willyanti Soewondo ◽  
Sidik ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Therapeutic Intervention ◽  
Tongue Cancer ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Garcinia Mangostana ◽  
Anti Cancer ◽  
Cancer Activity

Production of IL-8 primarily promotes angiogenic responses in cancer cells, which lead to favorable disease progression. Suppressing this production may, therefore, be a significant therapeutic intervention in targeting tumor angiogenesis. This study aimed to evaluate the reduction effects of xanthones in cancer cell lines. Nine known prenylated xanthones (1–9), isolated from the pericarp of Garcinia mangostana Linn (GML), were tested for their ability to suppress IL-8 (interleukin-8) of the SP-C1 (Supri's Clone 1) tongue cancer cell line. Of these compounds, 8-hydroxycudraxanthone-G (4) suppressed IL-8 within 48 hours. This is the first report of 8-hydroxycudraxanthone G suppressing the production of IL-8 (45% at 15.7 μg/mL in 48 hours). These results suggest that the prolonged suppression of IL-8 production by cancer cell lines is concerned in the anti-cancer activity of 8-hydroxycudraxanthone.

scholarly journals ETHNOPHARMACOLOGICAL EVALUATION OF MEDICINAL PLANTS FOR CYTOTOXICITY AGAINST VARIOUS CANCER CELL LINES

2017 ◽  
Vol 9 (5) ◽  
pp. 198 ◽  
Author(s):  
Ruchi Singh Thakur ◽  
Bharti Ahirwar
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Fruit Juice ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Phytochemical Analysis ◽  
Phyllanthus Emblica ◽  
Hydroalcoholic Extract

Objective: To evaluate the cytotoxic potential of leaves and seeds of Hibiscus sabdariffa L., fruit juice of Phyllanthus emblica, rhizomes of Dryopteris cochleata and flowers of Caesalpinia decapetala (Roth) Alston along with the chemical profiling of the most toxic extract through Gas-mass spectroscopy-MS technique.Methods: The hydroalcoholic extract of the selected crude drugs was prepared by maceration method and the extracts were undergone through phytochemical analysis. The cytotoxic activity of the hydroalcoholic extract was performed against four cancer cell lines i.e. liver (HepG2), breast (MCF7), prostate (PC-3) and leukemia (HL60) using sulphorhodamine B assay. The hydroalcoholic extract of Caesalpinia decapetala flowers was profiled through using gas mass spectroscopy.Results: The results confirmed that Phyllanthus emblica inhibited HL60 cancer cells at the dose of 35.6 µg/ml and show dose-dependent growth inhibition. The flowers of Caesalpinia decapetala inhibited nearly fifty percent of HL60 cancer cells at very low dose i. e 10 µg/ml. The analysis of Caesalpinia decapetala flowers shows the presence of diterpenoid furanolactones, bufadienolides, polycyclic enones, and androsterone.Conclusion: The fruit juice of Phyllanthus emblica and flowers of Caesalpinia decapetala showed good inhibitory activity against HL60 cancer cell line. The use of Phyllanthus emblica in herbal medicine is justified. The data obtained impelled to further assess the in vivo efficacy of Caesalpinia decapetala flowers for anticancer activity.

scholarly journals Cytotoxic and Anti-Plasmodial Activities of Stephania dielsiana Y.C. Wu Extracts and the Isolated Compounds

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3755 ◽  
Author(s):  
James Knockleby ◽  
Bruno Pradines ◽  
Mathieu Gendrot ◽  
Joel Mosnier ◽  
Thanh Tam Nguyen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
M Cell ◽  
Traditional Use ◽  
Aurora Kinases ◽  
Highly Effective

Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from Stephania dielsiana Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine (1) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC50 values ranging from 1.66 to 4.35 μM. Morever, oxostephanine (1) is on average two-fold more active against cancer cells than stephanine (3), having a similar chemical structure. Cells treated with oxostephanine (1) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine (1) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine (1), thailandine (2) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine (2) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 Plasmodium falciparum strains. The structure–activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of Stephania dielsiana Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs.

scholarly journals Galectin-3 Stimulates Tyro3 Receptor Tyrosine Kinase and Erk Signalling, Cell Survival and Migration in Human Cancer Cells

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1035
Author(s):  
Nour Al Kafri ◽  
Sassan Hafizi
Keyword(s):  
Cell Migration ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Tyrosine Kinases ◽  
Human Cancer ◽  
Serum Starvation ◽  
Human Cancer Cell Lines ◽  
Galectin 3

The TAM (Tyro3, Axl, MerTK) subfamily of receptor tyrosine kinases (RTKs) and their ligands, Gas6 and protein S (ProS1), are implicated in tumorigenesis and chemoresistance in various cancers. The β-galactoside binding protein galectin-3 (Gal-3), which is also implicated in oncogenesis, has previously been shown to be a ligand for MerTK. However, the selectivity of Gal-3 for the other TAM receptors, and its TAM-mediated signalling and functional properties in cancer cells, remain to be explored. The present study was aimed at determining these, including through direct comparison of Gal-3 with the two canonical TAM ligands. Exogenous Gal-3 rapidly stimulated Tyro3 receptor phosphorylation to the same extent as the Tyro3 ligand ProS1, but not Axl, in the cultured human cancer cell lines SCC-25 (express both Tyro3 and Axl) and MGH-U3 (express Tyro3 only). Gal-3 also activated intracellular Erk and Akt kinases in both cell lines and furthermore protected cells from acute apoptosis induced by staurosporine but not from serum-starvation induced apoptosis. In addition, Gal-3 significantly stimulated cancer cell migration rate in the presence of the Axl blocker BGB324. Therefore, these results have shown Gal-3 to be a novel agonist for Tyro3 RTK, activating a Tyro3-Erk signalling axis, as well as Akt signalling, in cancer cells that promotes cell survival, cell cycle progression and cell migration. These data therefore reveal a novel mechanism of Tyro3 RTK activation through the action of Gal-3 that contrasts with those of the known TAM ligands Gas6 and ProS1.

scholarly journals In vitro photodynamic treatment of cancer cells induced by aza-BODIPYs

2020 ◽  
Vol 19 (6) ◽  
pp. 790-799
Author(s):  
Miryam Chiara Malacarne ◽  
Stefano Banfi ◽  
Enrico Caruso
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Iodine Atom ◽  
Human Cancer ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Photodynamic Treatment ◽  
Human Cancer Cell Lines

Two new aza-BODIPY photosensitizers featuring an iodine atom on each pyrrolic unit of their structure, were synthesized in fairly good yields and tested in vitro on two human cancer cell lines to assess their photodynamic efficacy.

Sign in / Sign up

Export Citation Format

Share Document