scholarly journals Cytotoxic Synergism between a Proprietary Commiphora mukul Gum Extract GU-MCT810, 2-deoxy-D-glucose, and Metformin in Human Alveolar Rhabdomyosarcoma and Hepatoma Cell Lines In vitro

Author(s):  
Cheppail Ramachandran ◽  
Karl-Werner Quirin ◽  
Steven J. Melnick

In this investigation we have analyzed the synergism for the cytotoxic effect of a proprietary guggul gum extract (GU), 2-deoxy-D-glucose (2-DG) and metformin (Met) in SJRH30 human alveolar rhabdomyosarcoma and HepG2 hepatoma cell lines in vitro. 2-DG and Met as single agents have weak cytotoxic effects in both cell lines. However, the combination of GU+2-DG, GU+Met and 2-DG+Met showed synergism for cytotoxic effect by CompuSyn analysis. Therefore, GU can be included in the combination of drugs involving 2-DG and Met to have synergistic effect. GU also showed a dose-dependent increase in cellular glucose uptake in HepG2 cells like the antidiabetic drug 2,4-thiozolidine dione (TZ). The demonstration of synergism of anticancer effects between GU, metformin and 2-DG, suggest that their mechanisms are in general complementary, though further studies are required to delineate the mechanism of GU, 2-DG and metformin combinations.

1988 ◽  
Vol 16 (1) ◽  
pp. 32-37
Author(s):  
Margherita Ferro ◽  
Anna Maria Bassi ◽  
Giorgio Nanni

Two hepatoma cell cultures were examined as in vitro models to be used in genotoxicity and cytotoxicity tests without the addition of bioactivating enzymes. The MH1C1, and HTC hepatoma lines were used in this study to establish their sensitivity to a number of xenobiotics, namely, cyclophosphamide (CP), the classical positive control in bioactivation tests; benzaldehyde (BA), a short-chain aldehyde; and 4-hydroxynonenal (HNE), a major toxic end-product of the peroxidative degradation of cell membrane lipids. As a first approach, we compared the following cytotoxicity tests: release of lactate dehydrogenase (LDH), and colony formation efficiency (CF). Colony-forming cells were exposed to the drugs according to different procedures, before or after the anchorage phase. The leakage of LDH into the medium following exposure of both cell lines to HNE, CP and BA for up to 24 hours was found not to be a good index of cytotoxicity. A better indicator of cytotoxicity was CF, as evaluated by exposure of the cells 24 hours after seeding. The effects were detectable at very low concentrations, corresponding to 10, 90 and 100μM for HNE, CP and BA, respectively. The impairment of CF efficiency was dose-dependent and time-dependent, and several differences between the two cell lines were observed.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 247-247
Author(s):  
Marc Pracht ◽  
Nicolas Lepareur ◽  
Julien Edeline ◽  
Laurence Lenoir ◽  
Valerie Ardisson ◽  
...  

247 Background: In case of non resectable HCC, radioembolization and sorafenib (S) are therapeutic options respectively for intermediate and advanced stages. In some other cancers, there is an increase of efficacy when external beam radiotherapy is done concomitantly with systemic chemotherapy or targeted therapies. So we wondered if there could be a synergistic or an additive activity when S is combined with a radionuclide. Methods: Hepatoma cell lines N1S1 (murine HCC), HepG2 (human hepatoblastoma) and HepaRG (human HCC) were treated with increasing concentrations of rhenium-188 (188Re) or S. On each cell line, we have studied the cellular toxicities of S and 188Re using Tetrazolium dye test, extra-cellular medium LDH level and morphologic analysis. This was done for different dosage of S and 188Re. We measured the lethal concentration killing 25% of cells (LC25) with the results of the Tetrazolium dye test. Secondly, we looked for synergy or additivity on cellular toxicity of these two compounds according to cell lines by combined treatment. Synergy or additivity was estimated with the combination index (CI) method (synergy if CI lower than 1, additivity if CI = 1, antagonism if CI upper to 1) based on the Tetrazolium dye test’s results. Results: Monotherapy dose-dependent toxicities were observed for all three cell lines with 188Re and for the N1S1 and HepG2 cell lines only with S. Combined treatment with 188Re and S showed synergy on HepaRG and N1S1 cell lines and additivity on the HepG2 cell line. Conclusions: The additive, and even synergistic, interest of a combined treatment with 188Re and S is demonstrated in vitro (for the first time to our knowledge) on hepatoma cell lines. This results, in particular for the HepaRG cell line (human HCC), could be explained by the down-regulation of the hepatic drug transporters which are responsible for the Sorafenib efflux in case of simultaneous DNA damages due to a radionuclide exposition. This promising approach now needs to be confirmed in vivo. [Table: see text]


1988 ◽  
Vol 41 (2) ◽  
pp. 309-314 ◽  
Author(s):  
Gilles F. Alberici ◽  
Marc Pallardy ◽  
Luc Manil ◽  
Jean-Jacques Dessaux ◽  
Jacqueline Fournier ◽  
...  

Blood ◽  
1990 ◽  
Vol 75 (6) ◽  
pp. 1311-1318 ◽  
Author(s):  
RJ Ford ◽  
A Goodacre ◽  
I Ramirez ◽  
SR Mehta ◽  
F Cabanillas

B-cell non-Hodgkin's lymphomas (NHL-B) have been difficult to establish in long-term cell culture using standard techniques. We report the establishment of five representative cell lines from high grade NHL-B using B-cell growth factor (BCGF). The five NHL-B cell lines display the morphologic, immunophenotypic, genotypic, and biologic characteristics of the lymphoma cells present in the original diagnostic specimen. The cell lines showed at least a sevenfold dose- dependent increase in proliferation in vitro over background in the presence of BCGF. Other putative B-cell growth-stimulating cytokines showed no significant proliferative activity or were inhibitory in some cases. NHL-B cell lines secreted growth factor(s) into culture supernatants that mediated at least a fivefold dose-dependent increase in cell proliferation in autochthonous lymphoma cells and a 10-fold or greater stimulation in growth factor-dependent normal B cell lines in vitro. The cell lines show monoclonal rearrangements of IgH genes and nonrandom chromosomal abnormalities characteristic of NHL-B, while the expression of Epstein-Barr virus associated antigen (EBNA-I) is present in two of the five cell lines. The studies show that lineage-specific growth factors may be used to establish neoplastic B cell lines in vitro, which are important experimental systems for cellular and molecular studies in the NHL-B.


2013 ◽  
Vol 60 (4) ◽  
Author(s):  
Katarzyna Wierzbicka-Bregier ◽  
Wojciech Brutkowski ◽  
Anna Borkowska ◽  
Krzysztof Milewski ◽  
Krzysztof Zabłocki

Studies on insulin resistance of liver cells are often performed with the use of various hepatoma cell lines. Such an approach allows investigating selected biochemical pathways at the cellular level. However, possible modifications of metabolic processes due to the neoplastic nature of such cells must be considered. Expanding the diversity of hepatoma cell lines used in metabolic studies could deliver new data for comparison with those obtained for other cell lines and should reduce the risk of misleading conclusions. In this study rat hepatoma AS-30D cells were tested as a potential model for studies on palmitate-induced insulin resistance. It was found that insulin-induced Akt kinase phosphorylation was substantially reduced in cells incubated with palmitate at a concentration as low as 75 µM. This effect was not accompanied by excessive reactive oxygen species (ROS) generation or increased Jun N-terminal kinase (JNK) phosphorylation. Moreover, preincubation of AS-30D cells with rosiglitazone, an antidiabetic agonist of peroxisome proliferator-activated receptor gamma (PPARγ), efficiently prevented the palmitate-induced insulin resistance. We conclude that AS-30D hepatoma cells may be used as a model sensitive to insulin and vulnerable to palmitate-induced insulin resistance.


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