Lines cytotoxic effect

These complexes show considerable in vitro cytotoxic effects against various tumor cell lines [70, 71[. Moreover, the cationic complexes [Au(N,N, N")Cl[Cl are able to intercalate into ct DNA [71[. Gold(III) amidate complexes of histidine containing... 

A considerable amount of the gold that accumulates in the kidneys and liver of mammalian species is bound to MTs. This buildup of gold in the kidneys is accompanied by elevated levels of renal copper to form copper-rich, gold-bearing MTs. In cell lines that overproduce MT, there is commonly a resistance to the cytotoxic effects of gold compounds. This resistance is also seen often in parent lines that have been repeatedly exposed to gold complexes. The mechanisms of resistance include but are not limited to enhanced biosynthesis of MT [102]. 

Initial classification of some cytokines was also undertaken on the basis of the specific biological activity by which the cytokine was first discovered (e.g. TNF exhibited cytotoxic effects on some cancer cell lines CSFs promoted the growth in vitro of various leukocytes in clumps or colonies). This, too, proved an unsatisfactory classification mechanism, as it was subsequently shown that most cytokines display a range of biological activities (e.g. the major biological function of TNF is believed to be as a regulator of both the immune and inflammatory response). More recently, primary sequence analysis of cytokines coupled to determination of secondary and tertiary structure reveal that most cytokines can be grouped into one of six families (Table 8.2). 

Vincristine resistance has been studied in Chinese hamster ovary cell lines cells resistant to vincristine also are resistant to vinblastine and vindesine. Suggestions were made that, in cells with relatively low levels of drug resistance, at least two prominent mechanisms of resistance can occur (22). In the first instance, cellular resistance may be attributable to membrane alterations that are reversible, functionally, by treatment with verapamil. In the second, resistance has been postulated to be due to an altered sensitivity of tubulin to the effects of the drugs the primary basis for postulating an altered interaction with tubulin was that a subgroup of cells resistant to vincristine showed enhanced sensitivity to taxol, a drug that can stabilize microtubules. It should be emphasized that differential sensitivities of tubulins from different tumor cells to the effects of vincristine or vinblastine has been proposed as a basis for the susceptibilities of cells to the cytotoxic effects of such drugs (23). Differences have been described in the electrophoretic patterns for tubulins obtained from vin-... 

Chamberlain, M., and R. C. Brown (1978). The cytotoxic effects of asbestos and other mineral dust in tissue culture cell lines. Br. J. Exper. Pathol. 59 183— 188. 

A variety of mammalian cell culture systems can be used to detect mutations induced by chemical substances. The L5178Y mouse l)nnphoma line, measuring mutation at the TK locus, is preferred. TK is an important enz)une involved in DNA synthesis. Cells are exposed to the test substance at various concentrations, in the presence and absence of a metabolic activation system, for a suitable period of time, and then subcultured to assess cytotoxicity and to allow phenotypic expression prior to mutant selection. Cells deficient in TK because of a forward mutation are resistant to the cytotoxic effects of pyrimidine analogues (antimetabolites), such as trifluorothymidine (TFT). This is because the antimetabolites cannot be incorporated into cellular nucleotides and kill the cell through inhibition of cellular metabolism. After treatment, cells are grown in a medium containing TFT mutant cells can proliferate in the presence of TFT, whereas normal cells containing TK are killed. This allows the detection of an increase in mutant... 

Wadler S, Wersto R, Weinberg V, et al. Interaction of fluorouracil and interferon in human colon cancer cell lines Cytotoxic and cytokinetic effects. Cancer Res 1990 50 5735-5739. 

In addition to the above-outlined cytotoxic effects of gemcitabine, it also serves to act as a radiation sensitizer in many cell lines (see Table 1). Depending on the cell line tested, the drug concentration, the schedule of administration, and the cell proliferative status (e.g., plateau vs exponential growth), relative enhancement ratios (RERs) in the range of 1.1-2.5 have been reported. There is no evidence that preferential radiosensitization occurs in more radioresistant cell lines. 

Novel mechanisms of interest include sensitizing hypoxic tumor cell lines to enhance radiotoxicity. Tirapazamine is a hypoxia-selective compound 1-2-fold greater in magnitude in comparison to mitomycin C or porfiromycin (84). Its mechanism of action results in a one-electron reduction inducing DNA double-strand breaks and cell death under hypoxic conditions. The free radical is oxidized back to the parent compound under aerobic conditions. When combined with the platinum compounds, the cytotoxic effects may be equivalent to that seen with five times the dose of cisplatin without the toxicities that would be encountered if actually administered (85). 

The dimers were studied more closely in HL-60 leukaemia and Jurkat cell lines, and it was found that they have activities comparable to the clinically nsed anticancer drng doxorubicin. In terms of general toxicity to normal cells, it was observed that dimers 115 and 116 were not toxic to lymphocytes at doses approaching 100 p,M. In preliminary studies, apoptotic cell death was observed on exposnre to these componnds and further studies are ongoing to elucidate the underlying mechanism of apoptosis. For purposes of comparison, the corresponding phosphate ester monomers 117 and 118 were prepared and proved to have no antitumour activity in the cell lines examined. This result is important, because it rules out any role of the phosphate ester functionality in mediating the observed cytotoxic effects and emphasizes the necessity for a bivalent unit. 

Cytotoxic effect. THC, in leukemic cell lines (CEM, HEL-92, and HL60) and in peripheral blood mononuclear cells, 6 hours after exposure induced apoptosis, even at one times the IC50. THC did not appear to act synergistically with cytotoxic agents. 

Our laboratories were the first to use CEPH family cell lines to demonstrate that a significant genetic component contributed to susceptibility to the cytotoxic effects of cisplatin, 5-FU and docetaxel (17,18). Dolan et al. estimated the heritability for susceptibility to cisplatin-induced cytotoxicity to be approximately 0.47 therefore sensitivity to the C5dotoxic effects of cisplatin is under appreciable genetic influence. Linkage analysis was performed and the strongest signal (lod 2.16, empirical /7-value 0.0005) was found on chromosome 1 at 44 cM (18). 

The cytotoxic effect of curcumin on gastric carcinoma cell lines has been established. In a study curcumin and 5-fluorouracil (5-FU) synergistically inhibited the growth of gastric carcinoma cells. In another study, curcumin reversed the MDR of a human gastric carcinoma cell line in correlation with a decrease in P-gp function and a promotion of caspase-3 activation [Anand et al., 2008]. 

Curcumin has also been found to interrupt the cell cycle, to have cytotoxic effects, and to have a role in antiproliferation and the induction of apoptosis in a hepatocarcinoma cell line. Curcumin is a potent inhibitor of phenol sulfotransferase (SULT1A1) in human liver and extrahepatic tissues [Vietri et al., 2003]. Curcumin inhibited the interleukin-6 (IL-6) production, histone acetyltransferase (HAT) activity, and API activation [Chen et al., 2003a] and prevented cell death and apoptotic biochemical changes, such as the... 

Lev-Ari S, Vexler A, Starr A, Ashkenazy-Voghera M, Greif J, Aderka D, Ben-Yosef R. 2007. Curcumin augments gemcitabine cytotoxic effect on pancreatic adenocarcinoma cell lines. Cancer Invest 25 411-418. 

Walters DK, Muff R, Langsam B, Born W, Fuchs B. 2007. Cytotoxic effects of curcumin on osteosarcoma cell lines. Invest New Drugs 26 289-297. 

A. Kupferberg, G. Teller, P. Behr, C. Leray, P.F. Urban and G. Vincendon, Effect of 7p-hydroxycholesterol on astrocyte primary cultures and derived spontaneously transformed cell lines cytotoxicity and metabolism, Biochim. Biophys. Acta 1013 (1989)231-238. 

Additional in vitro effects of feverfew include inhibition of histamine release from mast cells and granular components from leukocytes inhibition of smooth muscle contraction cytotoxic effects on human tumor cell lines and antimicrobial effects against gram-positive bacteria, yeasts, and filamentous fungi. 

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