Lidamycin, one of enediyne antitumor antibiotics, was isolated by our institute. It is the focus of intense due to its unique chemical structure and potent cytotoxicities to tumor cells in vivo and in vitro. In addition to cleavage of DNA, effect of lidamycin on apoptotic gene expressions and cytoskeleton may involve in its high activities. To further elucidate its mechanism, we have observed the effect of lidamycin on the above-mentioned factors in human hepatoma bel-7402 cells.
The gene expressions were determined by Northern blot and dot blotanalysis. The changes of microfilament and microtubule were detected by indirect immunofluorescent method and the apoptotic cells were detected with mitochondria-specific apoptotic dye Mitosensor.
The obvious increment of c-myc and c-fos gene expressions and the inhibition of N-ras gene expression in bel-7402 cells were observed following lidamycin treatment (0.1-10 nmol/L) for 8 h. The arrangement of microfilament in the cells became regular and was similar to nonmalignant normal cells, but there was no effect on microtubule when the bel-7402 cells were treated with lidamycin 10 nmol/L for 8 h. No apoptotic cells were detected with Mitosensor in the lidamycin-treated cells for 8 h.
Lidamycin at lower concentrations can markedly affect the expression of the apoptosis related genes and the distribution of the cytoskeleton in the hepatoma bel-7402 cells. The results are helpful to elucidate the molecular mechanism of potent cytotoxicities of lidamycin to tumor cells.
[Show abstract][Hide abstract] ABSTRACT: To validate a radioactivity assay, the TCA-RA method, for the measurement of C-1027 in serum and to evaluate its application in determination of pharmacokinetics of C-1027 in mice.
(125)I-C-1027 was prepared by the Iodogen method and separated by HPLC. The radioactivity assay was established and used to determine (125)I-C-1027 in mice at doses of 10, 50 and 100 microg/kg after precipitation with 20% trichloroacetic acid (TCA-RA method). Several pharmacokinetic parameters were determined after intravenous injection of (125)I-C-1027 to mice.
After intravenous injection of (125)I-C-1027 to mice, at doses of 10, 50 and 100 microg/kg; the apparent distribution volumes (V(d)) were 0.26, 0.31 and 0.33 L/kg; the biological half-lives (T(1/2)) were 3.10, 3.40 and 3.90 h; the areas under curve (AUC) were 18.41, 103.69 and 202.74 ng/h/mL; the elimination rate constants (K) were 1.04, 1.26 and 0.58/h; and the total body clearance (Cl) were 0.54, 0.48 and 0.49 L/kg/h, respectively.
TCA-RA is a sensitive, reliable and suitable method for the determination of (125)I-C-1027 in mouse serum.
World Journal of Gastroenterology 03/2005; 11(5):717-20. DOI:10.3748/wjg.v11.i5.717 · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the tissue distribution, urinary and fecal excretions of (125)I-lidamycin ((125)I-C-1027) in mice and its biliary excretion in rats.
The total radioactivity assay (RA method) and the radioactivity assay after precipitation with 200 mL/L trichloroacetic acid (TCA-RA method) were used to determine the tissue distribution, and the urinary and fecal excretions of (125)I-C-1027 in mice and its biliary excretion in rats.
Tissue concentrations reached the peak at the fifth minute after administration of (125)I-C-1027 to mice. The highest concentration was in kidney, and the lowest in brain at all test-time points. The organs of the concentrations of (125)I-C-1027 from high to low were kidney, lung, liver, stomach, spleen, uterus, ovary, intestine, muscle, heart, testis, fat, and brain in mice. The accumulative excretion amounts of 0-24 h, and 0-96 h after administration of (125)I-C-1027 were 68.36 and 71.64% in urine, and 2.60 and 3.21% in feces of mice, respectively, and the accumulative excretion amount of 0-24 h was 3.57% in bile in rats.
Our results reflect the characteristics of the tissue distribution, urinary and fecal excretions of (125)I-C-1027 in mice and the biliary excretion of (125)I-C-1027 and its metabolites in rats, and indicate that (125)I-C-1027 and its metabolites are mainly distributed in kidney, and excreted in urine.
World Journal of Gastroenterology 07/2005; 11(21):3281-4. · 2.37 Impact Factor
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