Cancer cell lines mouse lymphoma

Much less inhibition was found in the MCF7/MDR1 drug-resistant human breast cancer cell line in the presence of same carotenoids as were investigated earlier on the human MDR1 gene-transfected mouse lymphoma cells. As Table 5 shows the, rhodamine accumulation was enhanced only moderately from 1.1 to 2.2 fluorescence activity ratio, which means that the rhodamine uptake was enhanced from 10% to 120% in the human breast cancer cells. On the other hand, some carotenoids such as Zl-neoxanthin, mono-epoxy-a-carotene and 15,15-dehydro-diepoxy-/J-carotene were inactive (Table 5). 

We have examined the effects of llavonoids and isoflavonoids on the P-gp-and MRP- mediated MDR mechanisms in both mouse lymphoma and human breast cancer cell lines. The interactions of the drug transporters P-gp or MRP with flavonoids or isoflavonoids might be worth their use as anticancer agents, such as a single administration or a combination cancer therapy with cytotoxic agents such as mitomycin C (MMC). Differences in the activities of the P-gp and the MRP-mediated efflux pump could be found in the presence of flavonoids and isoflavonoids. 

The interaction of ellipticine derivatives with topoisomerase II enzymes in Plasmodium berghei (163), a parasite of mouse red blood cells, mouse lymphoma L5178Y cells (164), simian virus 40 CV-1 cells (165), Trypanosoma cruzi (166,167), and the human small-cell lung cancer cell line NCI N417 (168,169) has been studied. In the latter study, the highest in vitro activity in the topoisomerase II-DNA cleavage reaction and decatenation was observed for elliptinium (5) and datelliptium (384) (769). 

The mouse lymphoma test uses a mutated mouse cancer cell line in which a partially damaged gene exists. When this gene is completely damaged, this mutated cell line is able to survive and replicate in the presence of a particular chemical. The cells are incubated within that chemical after exposure to the test article. If an increase in viability is detected, it would indicate that the test article was able to inactivate totally or damage the gene. 

The choice of a cell line to study MDR modulator potency was very important for future potential application in human cancer treatment. PhM (12) that were quite effective in resistant mouse lymphoma cells were only slightly active in drug-resistant human sarcoma cell line MES-SA/Dx5 [198]. The drug-sensitive human sarcoma cell line MES-SA and its multidrug-resistant counterpart MES-SA/Dx5 were applied as a model system for evaluation of MDR modulator activities. Examination performed by the flow cytometric Rhl23 accumulation test demonstrated that the well-known P-gp modulators verapamil (79) and TFP (5) reduced MDR in MES-SA/Dx5 cells. In resistant MES-SA/Dx5 cells, verapamil (79) and TFP (5) restored the drug accumulation pattern which was typical for sensitive cells. However, the effectiveness of PhM (12) was very low. The most active compounds were derivatives with an H atom at position 2 of the phenothiazine ring, followed by Cl-substituted and CF3-substituted compounds. 

The comparison of the sensitivity of mouse lymphoma and human breast cancer MCF7 cell lines shows that the same human MDR1 gene-encoded P-gp... 

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