Antitumor activity- and gene expression-based profiling of ecteinascidin Et 743 and phthalascidin Pt 650  Eduardo J Martinez, E.J Corey, Takashi Owa 

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Antitumor activity- and gene expression-based profiling of ecteinascidin Et 743 and phthalascidin Pt 650 Eduardo J Martinez, E.J Corey, Takashi Owa Chemistry.
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Antitumor activity- and gene expression-based profiling of ecteinascidin Et 743 and phthalascidin Pt 650  Eduardo J Martinez, E.J Corey, Takashi Owa  Chemistry & Biology  Volume 8, Issue 12, Pages 1151-1160 (December 2001) DOI: 10.1016/S1074-5521(01)00082-5

Fig. 1 Structures of ecteinascidin 743 (Et 743) and phthalascidin (Pt 650). Chemistry & Biology 2001 8, 1151-1160DOI: (10.1016/S1074-5521(01)00082-5)

Fig. 2 IC50 mean graphs and COMPARE analysis. Based on the MTT assay data, the IC50 value of each test drug was determined by the least-squares method. The arithmetic mean of the log IC50 values for all 36 cell lines was then calculated for each compound. The delta value of each cell line, defined as the difference between the logarithm of the cell line IC50 and the mean, was also calculated. The mean graph was constructed by projecting bars to the right or left of the mean, depending on whether cell sensitivity to a compound was more or less than average. All graphs were illustrated with the length of a bar proportional to the delta value. The Pearson product moment correlation coefficients for each set of delta value pairs between two test compounds were determined by using a statistical program. The correlation data between Et 743 and other drugs are presented here. Chemistry & Biology 2001 8, 1151-1160DOI: (10.1016/S1074-5521(01)00082-5)

Fig. 3 Time-course profiles of the drug effect on HCT116 cell growth. The experiment was carried out in triplicate with each of Et 743 and Pt 650 at 2.0 nM. The initial cell number was 1.0×106 cells per well (2.0 ml). The relative cell numbers at time points of 0, 12, 24 and 48 h are plotted in a semi-logarithmic graph. The plotted values represent the means of three independent data. Chemistry & Biology 2001 8, 1151-1160DOI: (10.1016/S1074-5521(01)00082-5)

Fig. 4 Flow cytometric cell cycle analysis. The effects of Et 743 and Pt 650 on cell cycle progression were examined according to the procedure described in Section 4. HCT116 cells were treated with 2.0 nM of each compound for 12 or 24 h. DNA histograms from drug-treated and untreated cells are shown here. Chemistry & Biology 2001 8, 1151-1160DOI: (10.1016/S1074-5521(01)00082-5)

Fig. 5 Average difference scatter correlation graphs. The transcription profiles of Et 743 and Pt 650 were compared in two cancer cell lines HCT116 colon and MDA-MB-435 breast. Average difference change values for all gene probes were calculated as the means of two independent values from duplicate array experiments. The means more than 50 for both compounds before antibody amplification are plotted in scatter correlation graphs for HCT116 and MDA-MB-435. These were also used after eliminating the data sets of the genes absent (designated A) in both control and drug-treated cells, yielding the Pearson product moment correlation coefficients between Et 743 and Pt 650. Chemistry & Biology 2001 8, 1151-1160DOI: (10.1016/S1074-5521(01)00082-5)

Fig. 6 Venn diagrams comparing sets of up- and down-regulated genes. In HCT116 colon and MDA-MB-435 breast cancer cells, induced or repressed genes with each of Et 743 and Pt 650 were determined based on the following criteria of the Affymetrix software algorithm: (i) fold change, ≥2.0 or ≤−2.0; (ii) differential call, I (increase) or D (decrease); (iii) absence call, genes except those displaying A (absent) in both control and drug-treated cells; (iv) genes satisfying all of (i)–(iii) in the data set either before or after antibody amplification; and (v) genes satisfying all of (i)–(iv) in both data sets taken in duplicate. Chemistry & Biology 2001 8, 1151-1160DOI: (10.1016/S1074-5521(01)00082-5)

Chemistry & Biology 2001 8, 1151-1160DOI: (10 Chemistry & Biology 2001 8, 1151-1160DOI: (10.1016/S1074-5521(01)00082-5)

Chemistry & Biology 2001 8, 1151-1160DOI: (10 Chemistry & Biology 2001 8, 1151-1160DOI: (10.1016/S1074-5521(01)00082-5)