Different human cancer cell lines

In one recent example of gene expression for pharmacological analysis, Scherf et al. [102] treated 60 different human cancer cell lines with 60,000 compounds. These same 60 cell lines were analyzed by expression analysis [103], and the cell lines were clustered based on expression profiles. The clusters were significantly different from those based on their response to drugs. 

Rhenium tricarbonyl complexes containing substituted cyclopentadi-enyl and bis diphenylphosphine ligands also were investigated as anticancer agents. The antiproliferative effects on breast cancer of complex A shown in Fig. 23 were examined relative to the known active metabolite, 4-hydroxy tamoxifen, and found to have a similar effect [107]. The cytotoxicity of five rhenium tricarbonyl bis-diphenylphosphine complexes B shown in Fig. 23 was examined for 18 different human cancer cell lines. The tests showed that all the complexes were active against specific tumor cell lines, especially a line of breast and uterine cancer [108]. 

A triorganotin quinolizidine compound, triethyitin Iupinyisulfide hydrochloride (Figure 4.4.7), has been reported to show quite good solubility in ethanol/water and to be a potent anti-proliferative against three different human cancer cell lines teratocarcinoma of the ovary (PA-1), colon carcinoma (HCT-8), and glioblastoma (A-172).2 The cytocidal effects due to this compound seem consistent with necrosis or delayed cell death rather than apoptosis. 

A series of anthraquinones has been chemically synthethized and the influences of structural features, such as the different functionalities in the nucleus have been studied in relation to cytotoxicity toward neoplastic cells. l,3-dihydroxy-9,10-anthraquinone synthetic derivatives were tested in vitro for inhibition against several different human cancer cell lines. Structure-activity analysis indicates that epoxidation of the hydroxyanthraquinone increased cytotoxicity against tumor cells, but ring-opening of the epoxide... 

Porta, C. et ah. Antioxidant enzymatic system and free radicals pathway in two different human cancer cell lines, H r/ca cer Res., 16 (5A), 2741,1996. 

Very recently, MacMillan et al. applied an intermolecular combined Friedel-Crafts-type conjugate addition/cyclization procedure as a key step in the total synthesis of diazonamide A (297) (271). Diazonamides are secondary metabolites isolated from the marine ascidian Diazona sp. (272, 273). Diazonamide A (297) was found to be a potent antimitotic member of this structurally unique family, exhibiting low nanomolar G/50 values towards different human cancer cell lines (272, 274). The unique structure of two 12-membered macrocycles that are conjoined through a triaryl-substituted quaternary stereogenic center (C-10) that is embedded in a furanoindoline core makes this compound a very interesting and... 

Epigallocatechin gallate have been shown to inhibit COX-2 and iNOS expression by preventing NF-kB activation [103]. Oligomers of 5-12 subunits, with the most powerful pentamers, are active on different human cancer cell lines [104]. 

Torreyanic acid, a selectively cytotoxic quinone dimer from the endophytic fungus Pestalotisopsis microspora, was first isolated by Clardy and his co-workers in 1996. The natural product was found to be cytotoxic against 25 different human cancer cell lines.In addition, torreyanic acid was found to be 5 to 10 times more potent than protein kinase C (PKC) agonists, 12-(9-tetradecanoyl phorbol-13-acetate (TPA), and was shown to cause cell death via apoptosis. 

This protocol could be extended to a range of different ,/i-unsaturated carbonyl compounds and either activated or deactivated aryl iodides [22], An application of related Heck chemistry to the synthesis of methylated resveratrol (3,4, 5-trihydroxy-( )-stilbene) is shown in Scheme 6.4 [23]. The phytoalexin resveratrol exhibits a variety of interesting biological and therapeutic properties, among them activity against several human cancer cell lines. Botella and Najera have shown that the trimethyl ether of resveratrol (Scheme 6.4) can be rapidly prepared by microwave-assisted Heck reaction of the appropriate aryl iodide and styrene derivatives, using the same oxime-derived palladacycle as indicated in Scheme 6.3. 

The cytotoxicity of taxoids 40-i and 40-S bearing the oxanorstatine residue were evaluated in our standard five human cancer cell line assay.71 As Table 7 shows, these two stereoisomers were found to possess considerably different cytotoxicity, which is rather unexpected. Taxoid 40-R showed a 3- to 10-fold increase in activity as compared to paclitaxel, while the other isomer, taxoid 40-S, exhibited a 2- to 4-fold decrease in activity, i.e. one to two orders of magnitude difference in activity is observed just by changing the stereochemistry of the epoxide moiety at C-3. This... 

Cytotoxicity of 3 -CF3-taxoids 71 and 72a-h thus obtained were evaluated against human cancer cell lines and the results are summarized in Table ll.45 As Table 11 shows, all these taxoids possess excellent activities, and are substantially more potent than either paclitaxel or docetaxel in virtually every case. The most remarkable results are, however, one order of magnitude better activities of the 10-acylated taxoids 72a-h as compared to paclitaxel and docetaxel against the drug-resistant breast cancer cell line, MCF7-R. The marked difference in cytotoxicity observed between 3 -(2-CF3-ethyl) taxoid, 68 or 69, and 3 -CF3-taxoids 72 reconfirms high sensitivity of the C-3 position to the size of substituent for the biological activity. 

Lecithin-based o/w MEs for parenteral use were formulated using polysorbate 80, IPM (Isopropyl myristate), lecithin, and water at different lecithin-polysorbate 80 weight ratios [115]. The formulated systems were shown to be highly stable and of minimal toxicity when evaluated in vitro. Phospholipid-based ME formulations of all-trans retinoic acid (ATRA) for parenteral administration were prepared and tested in vitro [116]. ATRA is effective against acute promyelocytic leukemia with highly variable oral bioavailability. Parenteral ME of ATRA was prepared using pharmaceutically acceptable ingredients, namely phospholipids and soybean oil. The inhibitory effect of ATRA on two human cancer cell lines (HL-60 and MCF-7) was not affected by incorporation into a ME formulation. 

No significant difference was observed in the survival rate of MCF7 treated with free-Doxorubicin or NP-doxorubicin. In contrast, for doxorubicin R MCF7, the IC50 for doxorubicin was 130-fold lower when NP-doxorubicin were used instead of free-doxorubicin. These results indicated that nanospheres provided an effective carrier for introducing a cytotoxic dose of doxorubicin into the pleiotropic resistant human cancer cell line Doxorubicin R MCF7. 

A., Eandi, M.R., Zara, M. and G.P. (2006) Intracellular accumulation and cytotoxicity of doxorubicin with different pharmaceutical formulations in human cancer cell lines. J. Nanosci. Nanotechnol,... 

Until 2002 our search for compounds with potential anticancer activity was restricted to those that were brine shrimp lethal and to serendipity. All of our new compounds are sent to the National Cancer Institute for screening against their battery of human cancer cell lines. Brine shrimp lethality is a reasonable indicator of cytotoxicity, so many cytotoxic compounds exhibit some degree of activity against certain human cancer cell lines. Compounds occasionally exhibit activity against a particular cancer cell line even if they are not cytotoxic. This is not at all unreasonable as anticancer activity can be a function of many different metabolic phenomena. We still routinely test all of our crude extracts, column fractions and pure compounds for brine shrimp lethality. Several studies have shown that most cancer chemotherapeutic agents exhibit brine shrimp... 

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