Idarubicin overcomes P-glycoprotein-related multidrug resistance: comparison with doxorubicin and daunorubicin in human multiple myeloma cell lines

Roovers, Dick J.; Vliet, Mariska van; Bloem, Andries C.; Lokhorst, Henk M.

doi:10.1016/s0145-2126(99)00041-7

Cited by 40 publications

(24 citation statements)

References 22 publications

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“…This may be related to its high lipophilicity, enabling easier intracellular penetration through the cell membrane composed of a double layer of lipids. Second, idarubicin has the ability to overcome the MDR system [24]. The MDR mechanism consists in pumping drugs out of cells and is classically observed in HCC [13,25,26].…”

Section: Discussionmentioning

confidence: 99%

Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Favelier

Boulin

Hamza

et al. 2012

Cardiovasc Intervent Radiol

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Background There is still no consensus about the best chemotherapeutic agent for transarterial chemoembolization (TACE). A recent in vitro study demonstrated that idarubicin, an anthracycline, was by far the most cytotoxic drug on human hepatocellular carcinoma (HCC) cell lines. Idarubicin is much more lipophilic than doxorubicin, leading to higher cell penetration through lipidic membranes and greater accumulation of the drug in the lipiodol. Furthermore, idarubicin has the ability to overcome multidrug resistance. Therefore, we designed this pilot human study to evaluate the safety and efficacy of lipiodol TACE using idarubicin. Methods In 21 consecutive patients treated by lipiodol TACE with idarubicin (10 mg) for HCC, safety data, tumor response (Response Evaluation Criteria in Solid Tumors, mRECIST), time to treatment failure (TTTF), and overall survival were evaluated. Results Postembolization syndrome was observed after 30.9 % (17 of 55) of sessions. No patient died from a TACE-related complication. No hematological grade 3-5 adverse event was observed. At least one grade 3 or higher adverse event occurred in 19 % (4 of 21) of patients. On imaging, no progression was encountered; four patients (24 %) exhibited stable disease, 12 (57 %) exhibited a partial response, and five (19 %) exhibited a complete response. Median TTTF was 16.7 months (Kaplan-Meier analysis). At 6 months, 94.7 % (95 % confidence interval [CI] 68.1-99.2) of patients did not reach treatment failure, whereas treatment failure was not reached in 50.6 % (95 % CI 21.6-73.9) of patients at 1 year. Overall survival was 83.5 % (95 % CI 57-94.4) at 1 year. Conclusion Idarubicin seems safe and effective in lipiodol TACE of HCC. This warrants further study to determine the potential of this drug to replace doxorubicin for TACE.

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Section: Discussionmentioning

confidence: 99%

Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Favelier

Boulin

Hamza

et al. 2012

Cardiovasc Intervent Radiol

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“…57 Purified myeloma plasma cells were seeded in a concentration of 1 × 10 6 /ml in a 96-well flat bottom plate (100 l/well) (Nunc, Roskilde, Denmark) and treated with 10 M ODNs. After 2, 4 or 7 days, 25 l of MTT (5 mg/ml) was added to each well.…”

Section: Viability Assaymentioning

confidence: 99%

Chemosensitization of myeloma plasma cells by an antisense-mediated downregulation of Bcl-2 protein

et al. 2003

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“…33 In short, cells were seeded in a concentration of 0.3 × 10 6 /ml for the plasma cell lines or 1 × 10 6 /ml for the purified myeloma cells and NBM mononuclear cells in a 96-well flat bottom plate (100 l/well) (Nunc, Roskilde, Denmark) and treated with different concentrations lovastatin (0, 1, 5, 10, 20, 40, 60, 80, 100 and 150 M). After 2 or 4 days, 25 l of MTT (5 mg/ml) was added to each well.…”

Section: In Vitro Cell Cultures Viability Assaymentioning

confidence: 99%

“…Membrane Pgp expression was determined by using the MRK16 antibody (kindly provided by Dr R Scheper) as described before. 33 The mean fluorescence ratio (MFR), defined as the ratio of the mean fluorescence intensities (MFI) of primary antibody and isotype control stained cells was used as a measure for the Bcl-2, Bax, LRP or Pgp protein expression.…”

Section: Expression Of Mdr-related Proteinsmentioning

confidence: 99%

The cholesterol lowering drug lovastatin induces cell death in myeloma plasma cells

et al. 2002

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Lovastatin is an irreversible inhibitor of HMG-CoA reductase and blocks the production of mevalonate, a critical compound in the production of cholesterol and isoprenoids. Isoprenylation of target proteins, like the GTP-binding protein Ras, is essential for their membrane localization and subsequent participation in intracellular signaling cascades. Lovastatin effectively decreased the viability of plasma cells from cell lines (n = 10) and myeloma patients' samples (n = 8) in a dose-and time-dependent way. Importantly, co-incubation of lovastatin with dexamethasone had a synergistic effect in inducing plasma cell cytotoxity. This effect was not the consequence of a change in the protein expression levels of Bcl-2 or Bax induced by lovastatin. The decrease in plasma cell viability was the result of induction of apoptosis and inhibition of proliferation. Mevalonate effectively reversed the cytotoxic and cytostatic effects of lovastatin in plasma cells. The cytotoxic activity of lovastatin was higher in Pgp expressing cell lines, but did not correlate with the multidrug resistance (MDR)-related proteins LRP, Bcl-2 and Bax. Lovastatin treatment resulted in a shift of Ras localization from the membrane to the cytosol that was reversed by mevalonate. The data presented in this paper warrant study of lovastatin alone or in combination with therapeutic drugs, in the treatment of myeloma patients.

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Idarubicin overcomes P-glycoprotein-related multidrug resistance: comparison with doxorubicin and daunorubicin in human multiple myeloma cell lines

Cited by 40 publications

References 22 publications

Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Lipiodol Trans-arterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin: First Experience

Chemosensitization of myeloma plasma cells by an antisense-mediated downregulation of Bcl-2 protein

The cholesterol lowering drug lovastatin induces cell death in myeloma plasma cells

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