In Vitro Cultivation of Human Tumor Tissues II. Morphological and Virological Characterization of Three Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

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Influence of New Synthetic Xanthones on the Proliferation and Migration Potential of Cancer Cell Lines In Vitro

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190405113519 ◽

2020 ◽

Vol 19 (16) ◽

pp. 1949-1965 ◽

Cited By ~ 1

Author(s):

Natalia Szkaradek ◽

Daniel Sypniewski ◽

Dorota Żelaszczyk ◽

Sabina Gałka ◽

Paulina Borzdziłowska ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Higher Plants ◽

Biological Activities ◽

Human Tumor ◽

Plant Metabolites ◽

Xtt Assay ◽

Treatment Protocols

Background: Natural plant metabolites and their semisynthetic derivatives have been used for years in cancer therapy. Xanthones are oxygenated heterocyclic compounds produced as secondary metabolites by higher plants, fungi or lichens. Xanthone core may serve as a template in the synthesis of many derivatives that have broad biological activities. Objective: This study synthesized a series of 17 new xanthones, and their anticancer potential was also evaluated. Methods: The anticancer potential was evaluated in vitro using a highly invasive T24 cancer cell line. Direct cytotoxic effects of the xanthones were established by IC50 estimation based on XTT assay. Results: 5 compounds of the total 17 showed significant cytotoxicity toward the studied cancer cultures and were submitted to further detailed analysis, including studies examining their influence on gelatinase A and B expression, as well as on the cancer cells migration and adhesion to an extracellular matrix. These analyses were carried out on five human tumor cell lines: A2780 (ovarian cancer), A549 (lung cancer), HeLa (cervical cancer), Hep G2 (liver cancer), and T24 (urinary bladder cancer). All the compounds, especially 4, showed promising anticancer activity: they exhibited significant cytotoxicity towards all the evaluated cell lines, including MCF-7 breast cancer, and hindered migration-motility activity of cancer cells demonstrating more potent activity than α-mangostin which served as a reference xanthone. Conclusion: These results suggest that our xanthone derivatives may be further analyzed in order to include them in cancer treatment protocols.

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Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽

10.3390/biomedicines9010092 ◽

2021 ◽

Vol 9 (1) ◽

pp. 92

Author(s):

Bashir Lawal ◽

Yen-Lin Liu ◽

Ntlotlang Mokgautsi ◽

Harshita Khedkar ◽

Maryam Rachmawati Sumitra ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Cancer Cell ◽

Human Tumor ◽

Cancer Cell Lines ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

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Synthesis and Characterization of New Palladium(II) Complexes with Ligands Derived from Furan-2-carbaldehyde and Benzaldehyde Thiosemicarbazone and their in vitro Cytotoxic Activities against Various Human Tumor Cell Lines

Zeitschrift für Naturforschung B ◽

10.1515/znb-2010-1015 ◽

2010 ◽

Vol 65 (10) ◽

pp. 1271-1278 ◽

Cited By ~ 4

Author(s):

Wilfredo Hernández ◽

Juan Paz ◽

Fernando Carrasco ◽

Abraham Vaisberg ◽

Jorge Manzur ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Human Tumor ◽

Myelogenous Leukemia ◽

Cytotoxic Activities ◽

Spectroscopic Techniques ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

With the ligands 4-phenyl-1-(furan-2-carbaldehyde)thiosemicarbazone, HTSC1, (1), 4-phenyl-1- (5´-phenyl-furan-2-carbaldehyde)thiosemicarbazone, HTSC2 (2), o-methoxy-benzaldehydethiosemicarbazone, HTSC3 (3), and o-cyano-benzaldehydethiosemicarbazone, HTSC4 (4), the corresponding palladium(II) complexes, Pd(TSC1)2 (5), Pd(TSC2)2 (6), Pd(TSC3)2 (7), and Pd(TSC4)2 (8) were synthesized and characterized by elemental analysis and spectroscopic techniques. The crystal structure of Pd(TSC3)2 (7) was determined by single-crystal X-ray diffraction. Complex 7 shows a squareplanar geometry, where two deprotonated ligands are coordinated to the PdII center through the nitrogen and sulfur atoms in a trans arrangement. In vitro antitumor studies against different human tumor cell lines have revealed that the palladium(II) complexes 5- 8 are more cytotoxic (IC50 values in the range of 0.21 - 3.79 μM) than their corresponding ligands (1 - 4) (> 60 μM). These results indicate that the antiproliferative activity is enhanced when thiosemicarbazone ligands are coordinated to the metal. Among the studied palladium(II) complexes, 8 exhibits high antitumor activity on K562 chronic myelogenous leukemia cells with a low value of the inhibitory concentration (IC50 = 0.21 μM).

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Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)77438-3 ◽

1990 ◽

Vol 265 (23) ◽

pp. 13933-13938 ◽

Cited By ~ 4

Author(s):

W.G. Stetler-Stevenson ◽

P.D. Brown ◽

M. Onisto ◽

A.T. Levy ◽

L.A. Liotta

Keyword(s):

Tumor Cell ◽

Mrna Expression ◽

Cell Lines ◽

Human Tumor ◽

Tissue Inhibitor Of Metalloproteinases ◽

Tumor Cell Lines ◽

Tissue Inhibitor ◽

Tumor Tissues

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Search for specific markers of neoplastic epithelial duct and myoepithelial cell lines established from human salivary gland and characterization of their growth in vitro

Cancer ◽

10.1002/1097-0142(19841215)54:12<2959::aid-cncr2820541225>3.0.co;2-5 ◽

1984 ◽

Vol 54 (12) ◽

pp. 2959-2967 ◽

Cited By ~ 47

Author(s):

Mitsunobu Sato ◽

Yoshio Hayashi ◽

Hideo Yoshida ◽

Tetsuo Yanagawa ◽

Yoshiaki Yura ◽

...

Keyword(s):

Salivary Gland ◽

Cell Lines ◽

Myoepithelial Cell ◽

Human Salivary Gland

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Cytogenetics of 52 human tumor cell lines grown in vitro

Cancer Genetics and Cytogenetics ◽

10.1016/0165-4608(86)90399-7 ◽

1986 ◽

Vol 19 (1-2) ◽

pp. 185

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Human Tumor ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

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NFB-01. FUNCTIONAL CHARACTERIZATION OF ATRX LOSS IN NF1-ASSOCIATED GLIOMA AND MPNST

Neuro-Oncology ◽

10.1093/neuonc/noaa222.605 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii417-iii418

Author(s):

Ming Yuan ◽

Karlyne Reilly ◽

Christine Pratilas ◽

Christopher Heaphy ◽

Fausto Rodriguez

Keyword(s):

Cell Lines ◽

Functional Characterization ◽

Tert Promoter ◽

Aggressive Tumors ◽

Sirna Knockdown ◽

Nih 3T3 ◽

Vitro Effect ◽

Murine Glioma

Abstract To identify the biologic relevance of ATRX loss in NF1-associated gliomagenesis, we studied the effects of Atrx loss using four previously characterized Nf1+/-Trp53+/- murine glioma lines. Lines 130G#3 and 158D#8 (corresponding to grade IV and III gliomas, respectively) displayed preserved ATRX protein expression compared to NIH-3T3 cells. We studied the effects of Atrx knockdown in these two lines in the presence and absence of the TERT inhibitor, BIRBR1532. Using a telomere-specific FISH assay, we identified increased signal intensity after Atrx knockdown, only in the presence of the TERT inhibitor. These features are reminiscent of ALT, although there were no significant alterations in cell growth. Next, we studied the effect of ATRX loss in MPNST lines ST88-14, NF90-8, STS-26T. These cell lines all expressed ATRX and DAXX. However, STS-26T contained a TERT promoter mutation and ST88-14 had a known SNP in the TERT promoter, while NF90-8 had no alterations. ATRX siRNA knockdown showed no significant effects in cell proliferation or apoptosis. However, ATRX knockdown resulted in rare ultra-bright foci, indicative of ALT. Next, we studied the in vitro effect of the ATR inhibitor VE-821 in MPNST cell lines. Only NF90-8 (lacking TERT alterations) demonstrated a decrease in growth after ATRX knockdown and VE-821 treatment. However, ATRX knockdown alone did not affect sensitivity to carboplatin. Our findings further support a role for ATRX loss with subsequent ALT activation in a biologic subset of NF1-associated malignancies, thereby opening an opportunity for therapeutic targeting of these aggressive tumors using specific classes of drugs.

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Synthesis and Biological Evaluation of Novel Triple-Modified Colchicine Derivatives as Potent Tubulin-Targeting Anticancer Agents

Cells ◽

10.3390/cells7110216 ◽

2018 ◽

Vol 7 (11) ◽

pp. 216 ◽

Cited By ~ 8

Author(s):

Urszula Majcher ◽

Greta Klejborowska ◽

Magdalena Kaik ◽

Ewa Maj ◽

Joanna Wietrzyk ◽

...

Keyword(s):

Cell Lines ◽

Anticancer Agents ◽

Binding Free Energy ◽

3D Structure ◽

Human Tumor ◽

Biological Evaluation ◽

Energy Estimates ◽

Colchicine Derivatives ◽

Mcf 7

Specific modifications of colchicine followed by synthesis of its analogues have been tested in vitro with the objective of lowering colchicine toxicity. Our previous studies have clearly shown the anticancer potential of double-modified colchicine derivatives in C-7 and C-10 positions. Here, a series of novel triple-modified colchicine derivatives is reported. They have been obtained following a four-step strategy. In vitro cytotoxicity of these compounds has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo, and LoVo/DX). Additionally, the mode of binding of the synthesized compounds was evaluated in silico using molecular docking to a 3D structure of β-tubulin based on crystallographic data from the Protein Data Bank and homology methodology. Binding free energy estimates, binding poses, and MlogP values of the compounds were obtained. All triple-modified colchicine derivatives were shown to be active at nanomolar concentrations against three of the investigated cancer cell lines (A549, MCF-7, LoVo). Four of them also showed higher potency against tumor cells over normal cells as confirmed by their high selectivity index values. A vast majority of the synthesized derivatives exhibited several times higher cytotoxicity than colchicine, doxorubicin, and cisplatin.

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