• Journal of Life Science
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• v.24 no.6
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• pp.700-706
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• 2014

Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

• Analytical Science and Technology
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• v.17 no.6
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• pp.470-475
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• 2004

The mercury film thin layer flow cell (MFTLFC) which yielded the highest sensitivity for the electrochemical reduction of doxorubicin was constructed by coating the glassy carbon working electrode (GCE; $A=0.208cm^2$) with $5{\mu}L$ of HgO coating solution (0.5% HgO + 0.25% polystyrene/cyclohexanone) and subsequently followed by applying a potential of -0.40 V for 300 sec in the flow stream of an acetate buffer of pH 4.5. The voltammogram of doxorubicin reached the diffusion current plateau at -0.53 V vs. a Ag/AgCl (3 M NaCl) in the MFTLFC. The diffusion current (Id) of doxorubicin at the MFTLFC was 1.7 times greater than the Id obtained at the TLFC employing a bare glassy carbon working electrode. When the peak areas (electric charge) were plotted vs. concentrations of standard anthracyclines, the calibration factors of doxorubicin and daunorubicin were $1.12{\times}10^8{\mu}C/M$ (coefficient of determination; $R^2$: 0.969) and $0.98{\times}10^8{\mu}C/M$> ($R^2$: 0.999), respectively in the concentration range between $1.0{\times}10^{-8}M$ and $1.0{\times}10^{-6}M$.

• Clinical and Experimental Pediatrics
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• v.50 no.8
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• pp.774-780
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• 2007

Purpose : The anthracyclines (AC) are widely used chemotherapeutic agents for pediatric cancers. However, the therapeutic use of these agents is limited by their cardiotoxicity. The aim of the present study was to investigate the usefulness of plasma B-type natriuretic peptide (BNP) levels as a marker for AC-induced cardiotoxicity compared to echocardiography in Korean children with cancer. Methods : Fifty-five pediatric cancer patients who had received chemotherapy including AC were enrolled. The cumulative AC doses, clinical symptoms, and two echocardiography parameters, left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF), were studied and compared with plasma BNP levels. Results : In 55 patients, plasma BNP levels were measured 115 times and echocardiographies were performed 64 times. The median cumulative dose of AC was $325mg/m^2$ (range 120-600; mean 345) and the median plasma BNP level was 10 pg/mL (range 5-950; mean 31). The cumulative AC doses correlated significantly with the plasma BNP levels (P=0.002). The plasma BNP levels correlated significantly with LVFS (P=0.018) and LVEF (P=0.025). Dilated cardiomyopathies were identified in three patients. LVFS and LVEF decreased and plasma BNP levels increased in a patient with acute dilated cardiomyopathy and in that with symptomatic chronic dilated cardiomyopathy. However, LVFS, LVEF and plasma BNP levels were normal in a patient with asymptomatic chronic dilated cardiomyopathy. Conclusion : The results of this study demonstrated that plasma BNP levels could be used as a marker for AC-induced cardiotoxicity; they showed good correlation with echocardiography findings in pediatric cancer patients. Plasma BNP levels may be used for the detection and management of AC-induced cardiotoxicity in Korean children with cancer.