Hsp90 inhibition by NVP-AUY922 and NVP-BEP800 decreases migration and invasion of irradiated normoxic and hypoxic tumor cell lines

2013 ◽  
Vol 331 (2) ◽  
pp. 200-210 ◽  
Author(s):  
Susanne Hartmann ◽  
Nadine Günther ◽  
Marlene Biehl ◽  
Astrid Katzer ◽  
Sebastian Kuger ◽  
...  
Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4350
Author(s):  
Jessica Castro ◽  
Giusy Tornillo ◽  
Gerardo Ceada ◽  
Beatriz Ramos-Neble ◽  
Marlon Bravo ◽  
...  

Despite the significant advances in cancer research made in recent years, this disease remains one of the leading causes of death worldwide. In part, this is due to the fact that after therapy, a subpopulation of self-renewing tumor cells can survive and promote cancer relapse, resistance to therapies and metastasis. Targeting these cancer stem cells (CSCs) is therefore essential to improve the clinical outcome of cancer patients. In this sense, multi-targeted drugs may be promising agents targeting CSC-associated multifocal effects. We have previously constructed different human pancreatic ribonuclease (RNase) variants that are cytotoxic for tumor cells due to a non-classical nuclear localization signal introduced in their sequence. These cytotoxic RNases affect the expression of multiple genes involved in deregulated metabolic and signaling pathways in cancer cells and are highly cytotoxic for multidrug-resistant tumor cell lines. Here, we show that these cytotoxic nuclear-directed RNases are highly selective for tumor cell lines grown in 3D, inhibit CSCs’ development and diminish the self-renewal capacity of the CSCs population. Moreover, these human RNase variants reduce the migration and invasiveness of highly invasive breast cancer cells and downregulate N-cadherin expression.


Planta Medica ◽  
2019 ◽  
Vol 85 (14/15) ◽  
pp. 1150-1159 ◽  
Author(s):  
Katrin Menke ◽  
Melanie Schwermer ◽  
Alexander Schramm ◽  
Tycho J. Zuzak

AbstractIn Europe, especially in German-speaking countries, administration of mistletoe extracts is the most common and popular complementary and alternative therapy approach reported in oncology. Mistletoe therapy is applied to children with cancer for curative and palliative therapeutic regimes with increasing frequency, but at the same time, there are only a few studies on the effectiveness of this therapy. Therefore, we have investigated the response of various pediatric cell lines (acute myeloid leukemia, Ewingʼs sarcoma, hepatocellular carcinoma, medulloblastoma, neuroblastoma, and osteosarcoma) to mistletoe extract, abnobaVISCUM Fraxini. Effects on cell proliferation, cell cycle distribution as well as on mitochondrial integrity and caspase-mediated apoptosis were investigated in neuroblastoma cell lines, SH-SY5Y and Kelly. Additionally, in vitro tumor cell migration and invasion were studied. In vivo effects of the mistletoe extract were investigated in a syngeneic neuroblastoma mouse model. We could show that tumor cell lines were from 5- to 640-fold more sensitive to abnobaVISCUM Fraxini treatment than non-tumorigenic fibroblasts, whereby neuroblastoma cell lines were the most sensitive. For two neuroblastoma cell lines, SH-SY5Y and Kelly, induction of caspase-9-mediated apoptosis, a decrease of mitochondrial integrity as well as attenuation of migration and invasion were observed. In vivo experiments revealed a reduction of tumor growth and a prolonged survival of tumor-bearing animals. In summary, we can state that these results provide the first preclinical data for cytotoxic activities of abnobaVISCUM Fraxini for a broad panel of pediatric tumor cell lines, in particular, neuroblastoma cells. Thus, it might be a potential remedy for the supportive treatment of neuroblastoma.


1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.


1989 ◽  
Vol 1 (6) ◽  
pp. 359-365 ◽  
Author(s):  
Richard D. H. Whelan ◽  
Louise K. Hosking ◽  
Alan J. Townsend ◽  
Kenneth H. Cowan ◽  
Bridget T. Hill

2006 ◽  
Vol 11 (3) ◽  
pp. 177-183 ◽  
Author(s):  
Kil-Nam Kim ◽  
Ki-Wan Lee ◽  
Choon-Bok Song ◽  
Chang-Bum Ahn ◽  
You-Jin Jeon

2020 ◽  
Vol 17 (4) ◽  
pp. 512-517
Author(s):  
Ognyan Ivanov Petrov ◽  
Yordanka Borisova Ivanova ◽  
Mariana Stefanova Gerova ◽  
Georgi Tsvetanov Momekov

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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