Cell lines testing

GlaxoSmithKline has filed patent applications covering 5-(benzimidazol-l-yl)thiophenes 111 and 112 and 2-(benzimidazol-l-yl)thioazoles 113 as inhibitors of PLK-1 [274,275]. Many potent compounds were claimed for 5-(benzimidazol-l-yl)thiophene series, including analog 111 with submicromolar inhibition against PLK-1 and anti-proliferative activity in five out of the six tumor cell lines tested. According to the data disclosed in the filing, a variety of substituents were accommodated on the 5- and 6-positions of the ben-... 

In the laboratory the immortal cell lines are those derived from cancer. The most famous is the HeLa cancer cells that many of us use as one of the cell lines tested against various anticancer agents. The name HeLa cells is derived from Henrietta Lacks, a black woman, who died from cervical cancer. The cells are so strong that they invade other cell lines, both healthy and other cancer cell lines, giving contaminated or mutated cell lines. HeLa cells have good telomerase levels. If antisense RNA is added to HeLa cells so that the RNA contains the opposite message to the ordinary RNA in the telomerase, the effect is that the telomerase is blocked and the HeLa cells are no longer immortal and die after about 25 replications. 

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. 

Current efforts favor tumor cell line tests, conducted by the National Cancer Institute (NCI) drug development program [62]. In the current NCI anticancer screen, each compound is tested against 60 human tumor cell lines derived from several cancer types (lung, colon, melanoma, kidney, breast, ovary, brain, leukemia). The tumor cells are seeded on 96-well microtiter plates and pre-incubated for 24 h. The test agents are then added to the wells (five 10-fold dilutions 0.01 -100 pmol/1) and are incubated for 48 h with the tumor cell lines. At the termination of the assay, the cells are fixed in situ with trichloroacetic acid (TCA), washed and dried. Sulforhodamine B (SRB), a dye that binds to the basic amino... 

This strategy has resulted in the discovery of nanomolar and even picomolar ATP-competitive ruthenium-based inhibitors for different protein kinases [146]. In particular one of these complexes DW1/2 (Chart 9) has shown remarkable anticancer properties in several cancer cell lines (300 nM of the complex maximally inhibited cell growth in most of the melanoma cell lines tested) [149]. 

Among 20 cell lines tested, CACO-2 cells were the only onces to differentiate spontaneously to intestinal enterocytes (Chantret et al. 1988). They resemble many characteristics of small intestinal epithelial cells (Hidalgo and Borchardt 1989) and are still the most widely accepted model in industry and academia (Artursson and Karlsson 1991 Artursson et al. 1996 Audus et al. 1990 Gan and Thakker 1997 Artursson and Borchardt 1997 and many others). Reduced demands for compound volumes in cellular assays allow for screening (Stevenson et al. 1995 Kuhfeld et al. 1994). CACO-2 cells predict permeability with reasonable accuracy and are used in many different test designs. 

MTS cytotoxicity data were collected for a comparison of (R,/ )-psorospermin with (R,R)-5-methoxy-psorospermin, (.R,S()-5-methoxy-psorospermin, (5, / )-5-methoxy-psorospermin, and (N,S()-5-methoxy-psorospermin in cell viability assays with various tumor cell lines. Test results are provided in Table 1. 

Isoflavonoids are also compounds that should be bom in mind for future cytotoxic studies with flavonoids. Isoflavones (aglycones with a 2-3 double bound, a 4 oxo group and the B-ring at C3 position) with the association of substituents mentioned above are not studied and could be. Besides, rotenoids are very cytotoxic isoflavonoids that are not well studied although one of them, 12a 3-hydroxyamorphigenin, is the most cytotoxic flavonoid found in our review, with values of less than 0.001 pg/mL on the six human cancer cell lines tested by Li et a/. [78]. 

A series of fifty-three isoquinoline alkaloids were tested for cytotoxicity against A-549 (human lung carcinoma), HCT-8 (human colon carcinoma), KB, P-388, and L-1210 cells in vitro. Liriodenine showed potent and wide spectrum activity against all five cell lines tested A-549 (EDJ0 0.72 pg/ml), HCT-8 (0.70), KB (1.00), P-388 (0.57), and L-121-0 (2.33)[299]. 

Garcinia kola Heckel (stem bark) GBi (176). GBi (176) exhibited a-glucosidase and aromatase inhibitory activities, as well as antiplasmodial activity, but was not toxic against cell lines tested. GB] (176) may be a potential dietary supplement or phytomedicine for the prevention of breast cancer and type 2 diabetes mellitus. Antia et ah, 2010[194]. 

The biflavones ginkgetin (7), isoginkgetin (13) and l-4 -0-methylrobustaflavone (65), isolated from the herb Selaginella moellendorffii Hieron, exhibited selective cytotoxicity against the three human cancer cell lines tested. [44]... 

Despite all these positive results, an in vitro study performed by Scheithauer et al. to investigate the combination of hyaluronidase with four cytostatics (doxorubicin, methotrexate, cis-platin and vinblastine) against six cell lines led to disappointing results [118]. However, it was observed that the combined drug-hyaluronidase effect does not depend on the class of anticancer agent used, and the sensitivity toward the combined effect was heterogeneous among the various tumor cell lines tested. 

Mammalian Cell Line Testing of Environmental Samples... 

As described in the section 3.1.1, the diterpenoids from S. dulcis showed relatively strong cytotoxicity against HaLa cells. In order to evaluate SDB as antitumor agent, the cytotoxic effects of SDB were examined in six human cell lines, i.e., HeLa 229, HeLa S3 and HEp-2 cells derived from tumor tissues and FL, Chang liver and intestine 407 cells derived from normal tissues. As summarized in Table 9, SDB showed potent cytotoxicity for the cell lines tested. It is notable that higher toxicity was observed in tumor cell lines than in normal cell lines. Similar tendency on the cell growth was also found when the effects of 5-fluorouracil (5-FU) on the cell growth of these cultures were examined. 

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