scholarly journals 5-Acetamido-1-(methoxybenzyl) isatin inhibits tumor cell proliferation, migration, and angiogenesis

RSC Advances ◽  
2019 ◽  
Vol 9 (63) ◽  
pp. 36690-36698
Author(s):  
Qian Zhang ◽  
Ying Fu ◽  
Yufan Zhao ◽  
Shanshan Cui ◽  
Jing Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Tumor Cell Lines ◽  
Tumor Cell Proliferation

5-Acetamido-1-(methoxybenzyl) isatin inhibited the proliferation, migration, and angiogenesis of several tumor cell lines in vitro.

An Automated Image Capture and Quantitation Approach to Identify Proteins Affecting Tumor Cell Proliferation

2004 ◽  
Vol 9 (3) ◽  
pp. 216-222 ◽  
Author(s):  
Kaumudi M. Bhawe ◽  
Robert A. Blake ◽  
Douglas O. Clary ◽  
Peter M. Flanagan
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Kinase Inhibitor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Functional Assay ◽  
Tumor Cell Lines ◽  
Tumor Cell Proliferation ◽  
Adenoviral Infection

To facilitate the characterization of proteins that negatively regulate tumor cell proliferation in vitro, the authors have implemented a high-throughput functional assay that measures S-phase progression of tumor cell lines. For 2 tumor cell lines—human melanoma A375 and human lung carcinoma A549—conditions were established using the cyclin-dependent kinase inhibitor, p27kip; the tumor suppressor p53, a kinase-inactive allele of the cell cycle-regulated serine/threonine kinase Aurora2; and the G1/S drug block, aphidicolin. For screening purposes, gene libraries were delivered by adenoviral infection. Cells were fixed and labeled by immunocytochemistry, and an automated image acquisition and analysis package on a Cellomics ArrayScan®II was used to quantify the effects of these treatments on cell proliferation. The assay can be used to identify novel proteins involved in proliferation and serves as a more robust, reproducible, and sensitive alternative to enzyme-linked immunosorbent assay (ELISA)-based technologies.

Enzastaurin a protein kinase Cbeta-selective inhibitor, inhibits the growth of SCLC and NSCLC cell lines

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13138-13138 ◽  
Author(s):  
E. Nakajima ◽  
B. Helfrich ◽  
D. Chan ◽  
Z. Zhang ◽  
F. R. Hirsch ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Selective Inhibitor ◽  
Nsclc Cell ◽  
Tumor Cell Proliferation ◽  
Potential Synergy

13138 Background: PKCβ is a member of the PKC family of serine-threonine protein kinases involved in tumor cell proliferation and apoptosis. Inhibition of PKCs induced differentiation and enhanced chemotherapy. PKCβ activation is required for tumor-induced angiogenesis. The PKCβ-selective inhibitor enzastaurin, originally developed as an antiangiogenic agent, inhibited tumor cell proliferation in prostate, colon and glioblastoma cell lines in vitro. In NSCLC lines, enhanced phosphorylation and altered PKC expression was demonstrated. In SCLC lines specific PKC isoforms were associated with cisplatin resistance. Methods: The growth inhibitory effects of enzastaruin were evaluated by 6-day MTT assays; the cell cycle effects by FACS analysis; the effects on downstream phophorylated signaling molecules by western blotting. Results: Enzastaurin inhibited the growth of 11 SCLC lines (IC50s 3–10 μM) and 4 NSCLC cell lines (IC50s 3–10 μM). An increase of 7–31% of cells in the G2/M phase of the cell cycle compared to untreated control was observed following 48 hour exposure to the IC50 dose of enzastaurin in both SCLC and NSCLC cell lines. PKCβ has been shown to phosphorylate both GSK3β and Akt. A 24-hour IC50 enzastaurin exposure significantly reduced phosphorylation of GSK3β (Ser9) in both SCLC and NSCLC lines. No changes were observed in phospho-AKT (Thr308) in either SCLC or NSCLC cell lines. Phospho-ribosomal protein S6 (Ser240/244) was also reduced in both SCLC and NSCLC cell lines. Potential synergy was studied between enzastaurin and pemetrexed in SCLC and NSCLC lines and the results were analyzed using the Calcusyn Program by Chou and Talalay. Synergistic (CI <1) to additive interactions were observed between pemetrexed (IC20–70) and enzastaurin (≤ IC50) in both SCLC lines (N = 3) and NSCLC lines (N = 2). Conclusions: We conclude that enzastaruin produces in vitro growth inhibition of SCLC and NSCLC cell lines through inhibition of GSK3β ser9 phosphorylation and has synergistic growth inhibition with pemetrexed. [Table: see text]

Cardiac Derived Stromal Cells Inhibit Tumor Cell Proliferation: A Potential Role Of miR206

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4861-4861
Author(s):  
Ian K. McNiece ◽  
Santhosh Sivajothi
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Stromal Cells ◽  
Cardiac Tissue ◽  
Tumor Cell Lines ◽  
Tumor Cell Proliferation ◽  
Inhibition Of Proliferation

Abstract Stromal cells play an important role in control of proliferation and differentiation of stem cells and are a key component of the stem cell niche. Bone marrow (BM) stromal cells (also termed mesenchymal stem cells; MSC) have been extensively studied and shown to control differentiation of hematopoietic stem cells (HSCs) in part through secreted growth factors. Recent studies have demonstrated the presence of stromal cells in cardiac tissue, however the role of cardiac stromal cells (CStrC) is unclear. In this study we have compared human CStrCs to human BM-MSCs and demonstrate that CStrCs have a similar morphology and surface marker expression as BM-MSCs. To further characterize the CStrCs we performed micro array analysis of human CStrCs compared to human BM-MSCs. The CStrCs expressed a distinct cytokine and cytokine receptor profile compared to BM-MSC. In addition, a number of micro RNAs were expressed at very high levels in CStrCs compared to BM-MSC. Cardiac- associated microRNAs, including miR-1, miR-133a, and miR-206 were expressed at higher levels in CStrCs compared to BM-MSC. Given the lack of tumor development in cardiac tissue we hypothesized that CStrCs would fail to support tumor cell growth which has been described for BM-MSCs. Therefore, we cultured human tumor cell lines on CStrCs and compared the tumor cell proliferation to BM-MSCs. CStrCs inhibited the proliferation of a range of tumor cell lines including myeloid cell lines HL60, K562, myeloma cell lines U-266, RPMI 8266, ARP-1 and the B cell line Raji, while BM-MSCs supported the proliferation of tumor cells. Further we tested media conditioned by CStrCs and demonstrated inhibition of proliferation of both cell lines. Previous studies have implicated miR-206 in inhibition of proliferation of tumor cells and given the high levels of expression of miR-206 in CStrCs we hypothesize that miR-206 is a key player in the inhibitory effects of CStrCs and this effect is mediated via secreted molecules. Disclosures: McNiece: Proteonomix Inc: Consultancy.

scholarly journals Processing of Proaugurin Is Required to Suppress Proliferation of Tumor Cell Lines

2011 ◽  
Vol 25 (5) ◽  
pp. 776-784 ◽  
Author(s):  
Akihiko Ozawa ◽  
Adam N. Lick ◽  
Iris Lindberg
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Secretory Pathway ◽  
Secretory Granules ◽  
Major Product ◽  
Metabolic Labeling ◽  
Tumor Cell Lines ◽  
Suppress Cell Proliferation

Abstract Augurin is a secretory molecule produced in pituitary, thyroid, and esophagus and implicated in a wide array of physiological processes, from ACTH release to tumor suppression. However, the specific proaugurin-derived peptides present in various cell types are not yet known. In order to shed light on the posttranslational modifications required for biological activity, we here describe the posttranslational processing of proaugurin in AtT-20 and Lovo cells and identify proaugurin-derived products generated by convertases. In vitro cleavage of proaugurin with proprotein convertases produced multiple peptides, including a major product with a mass of 9.7 kDa by mass spectrometry. Metabolic labeling of C-terminally tagged proaugurin in AtT-20 and AtT-20/PC2 cells resulted in a major 15-kDa tagged form on SDS-PAGE, which likely corresponds to the 9.7-kDa in vitro fragment, with the added tag, its linker, and posttranslational modification(s). The secretion of neither proaugurin nor this cleavage product was stimulated by forskolin, indicating its lack of storage in regulated secretory granules and lack of cleavage by PC2. Incubation of cells with the furin inhibitor nona-d-arginine resulted in impaired cleavage of proaugurin, whereas metalloprotease inhibitors did not affect proaugurin proteolysis. These data support the idea that proaugurin is cleaved by furin and secreted via the constitutive secretory pathway. Interestingly, proaugurin was sulfated during trafficking; sulfation was completely inhibited by brefeldin A. Proliferation assays with three different tumor cell lines demonstrated that only furin-cleaved proaugurin could suppress cell proliferation, suggesting that proteolytic cleavage is a posttranslational requirement for proaugurin to suppress cell proliferation.

Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

2020 ◽  
Vol 17 (4) ◽  
pp. 512-517
Author(s):  
Ognyan Ivanov Petrov ◽  
Yordanka Borisova Ivanova ◽  
Mariana Stefanova Gerova ◽  
Georgi Tsvetanov Momekov
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Biological Activities ◽  
Human Tumor ◽  
Mannich Bases ◽  
In Vitro Cytotoxicity ◽  
Tumor Cell Lines ◽  
Human Tumor Cell ◽  
Human Tumor 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.

Cytotoxic Effect of Brassica oleracea Extract on two Tumor Cell Lines in vitro

2013 ◽  
Vol 16 (1) ◽  
pp. 137-142
Author(s):  
Farooq I. Mohammed ◽  
◽  
Farah T. Abdullah ◽  
Shaimaa Y. Abdulfttah ◽  
◽  
...  
Keyword(s):  
Tumor Cell ◽  
Brassica Oleracea ◽  
Cell Lines ◽  
Cytotoxic Effect ◽  
Tumor Cell Lines

scholarly journals Combined Application of Pan-AKT Inhibitor MK-2206 and BCL-2 Antagonist Venetoclax in B-Cell Precursor Acute Lymphoblastic Leukemia

2021 ◽  
Vol 22 (5) ◽  
pp. 2771
Author(s):  
Anna Richter ◽  
Elisabeth Fischer ◽  
Clemens Holz ◽  
Julia Schulze ◽  
Sandra Lange ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Morphological Changes ◽  
Synergistic Effects ◽  
Lymphoblastic Leukemia ◽  
Tumor Cell Proliferation ◽  
Akt Inhibitor ◽  
Akt Phosphorylation ◽  
Combined Application

Aberrant PI3K/AKT signaling is a hallmark of acute B-lymphoblastic leukemia (B-ALL) resulting in increased tumor cell proliferation and apoptosis deficiency. While previous AKT inhibitors struggled with selectivity, MK-2206 promises meticulous pan-AKT targeting with proven anti-tumor activity. We herein, characterize the effect of MK-2206 on B-ALL cell lines and primary samples and investigate potential synergistic effects with BCL-2 inhibitor venetoclax to overcome limitations in apoptosis induction. MK-2206 incubation reduced AKT phosphorylation and influenced downstream signaling activity. Interestingly, after MK-2206 mono application tumor cell proliferation and metabolic activity were diminished significantly independently of basal AKT phosphorylation. Morphological changes but no induction of apoptosis was detected in the observed cell lines. In contrast, primary samples cultivated in a protective microenvironment showed a decrease in vital cells. Combined MK-2206 and venetoclax incubation resulted in partially synergistic anti-proliferative effects independently of application sequence in SEM and RS4;11 cell lines. Venetoclax-mediated apoptosis was not intensified by addition of MK-2206. Functional assessment of BCL-2 inhibition via Bax translocation assay revealed slightly increased pro-apoptotic signaling after combined MK-2206 and venetoclax incubation. In summary, we demonstrate that the pan-AKT inhibitor MK-2206 potently blocks B-ALL cell proliferation and for the first time characterize the synergistic effect of combined MK-2206 and venetoclax treatment in B-ALL.

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

Biomedicines ◽  
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.

Evaluation of ponatinib in vitro effect in three canine mast cell tumor cell lines expressing FGFR-1, PDGFR-α, and VEGFR-2

2021 ◽  
Vol 269 ◽  
pp. 105621
Author(s):  
C.J. Fisher ◽  
A.T. Lejeune ◽  
M.J. Dark ◽  
O.M. Hernandez ◽  
K. Shiomitsu
Keyword(s):  
Mast Cell ◽  
Tumor Cell ◽  
Cell Lines ◽  
Cell Tumor ◽  
Tumor Cell Lines ◽  
Mast Cell Tumor ◽  
Canine Mast Cell Tumor ◽  
Vitro Effect

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

2010 ◽  
Vol 65 (10) ◽  
pp. 1271-1278 ◽  
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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