Interaction of a doxorubicin-transferrin conjugate with isolated transferrin receptors

Ruthner, Monika; Bérczi, Alajos; Goldenberg, Hans

doi:10.1016/0024-3205(94)00575-3

Cited by 5 publications

(1 citation statement)

References 18 publications

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“…The exact mechanism of Tf-based enhancement of drug effect is still to be elucidated completely, but it is generally suggested to be due to enhanced cellular drug uptake and the effect on efflux transporters (P-gp). , Wang et al have shown that doxorubicin mainly accumulates in the cytoplasm around the nucleus in MCF-7/Adr cells; however, the Tf conjugate of doxorubicin-gallium accumulates in both the cytoplasm and nucleus of both the MCF-7/Adr and MCF-7 cells . Since doxorubicin works by intercalating nuclear DNA, its localization in the nucleus is necessary for therapeutic efficacy.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Antiproliferative Activity of Transferrin-Conjugated Paclitaxel-Loaded Nanoparticles Is Mediated via Sustained Intracellular Drug Retention

2005

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We studied the molecular mechanism of greater efficacy of paclitaxel-loaded nanoparticles (Tx-NPs) following conjugation to transferrin (Tf) ligand in breast cancer cell line. NPs were formulated using biodegradable polymer, poly(lactic-co-glycolide) (PLGA), with encapsulated Tx and conjugated to Tf ligand via an epoxy linker. Tf-conjugated NPs demonstrated greater and sustained antiproliferative activity of the drug in dose- and time-dependent studies compared to that with drug in solution or unconjugated NPs in MCF-7 and MCF-7/Adr cells. The mechanism of greater antiproliferative activity of the drug with conjugated NPs was determined to be due to their greater cellular uptake and reduced exocytosis compared to that of unconjugated NPs, thus leading to higher and sustained intracellular drug levels. The increase in antiproliferative activity of the drug with incubation time in MCF-7/Adr cells with Tf-conjugated NPs suggests that the drug resistance can be overcome by sustaining intracellular drug retention. The intracellular disposition characteristics of Tf-conjugated NPs following their cellular uptake via Tf receptors could have been different from that of unconjugated NPs via nonspecific endocytic pathway, thus influencing the NP uptake, their intracellular retention, and hence the therapeutic efficacy of the encapsulated drug.

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Section: Discussionmentioning

confidence: 99%

Enhanced Antiproliferative Activity of Transferrin-Conjugated Paclitaxel-Loaded Nanoparticles Is Mediated via Sustained Intracellular Drug Retention

2005

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Cytotoxic effects of a doxorubicin-transferrin conjugate in multidrug-resistant KB cells

Fritzer

Szekeres

Szüts

et al. 1996

Biochemical Pharmacology

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The plasma membrane NADH-diaphorase is active during selective phases of the cell cycle in mouse neuroblastoma cell line NB41A3. Its relation to cell growth and differentiation

Zurbriggen¹,

Dreyer²

1996

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Plasma membrane oxidoreductases have been described in all cells and use extracellular impermeant electron acceptors (DCIP, Ferricyanide) that are reduced by NADH. They appear to regulate the overall cell activity in response to oxidative stress from the cellular environment. An NADH-DCIP reductase has been described at the plasma membrane of NB41A3, a neuroblastoma cell line (Zurbriggen and Dryer (1993) Biochim. Biophys. Acta 1183, 513-520) whose activation with extracellular impermeant substrates promotes cell growth. Elutriation was performed to separate cells and the various fractions were analysed for enzyme activity on intact cells combined with flow cytometry. These studies showed that the enzyme is mostly induced and activated during the G1 and during the G2/M-phases. These observations were further corroborated with specific inhibitors of the cell cycle. A three-fold increase in enzyme activity was observed in the presence of alpha-amanitin, a specific cell cycle inhibitor of the G1-phase. Taxol, a specific inhibitor of the M-phase, also induces a significant increase in enzyme activity. FACS analysis of taxol -treated and alpha-amanitin-treated cells corroborated these data. The cells have been synchronized and the enzyme activity was measured at different time intervals. An activity increase was observed after ca. 2-3 h, that corresponds to a raise in the M-phase, according to FACS data. Furthermore, NTera-2 cells - a human neuroblastoma cell line that differentiates into fully mature neurones in the presence of retinoic acid - exhibit a 50% decrease in the enzyme activity during the G0-phase upon differentiation, compared to undifferentiated cells. Together the data presented in this paper show that this plasma membrane NADH-diaphorase affects cell growth and differentiation and is strongly modulated at various phases of the cell cycle.

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Interaction of a doxorubicin-transferrin conjugate with isolated transferrin receptors

Cited by 5 publications

References 18 publications

Enhanced Antiproliferative Activity of Transferrin-Conjugated Paclitaxel-Loaded Nanoparticles Is Mediated via Sustained Intracellular Drug Retention

Enhanced Antiproliferative Activity of Transferrin-Conjugated Paclitaxel-Loaded Nanoparticles Is Mediated via Sustained Intracellular Drug Retention

Cytotoxic effects of a doxorubicin-transferrin conjugate in multidrug-resistant KB cells

The plasma membrane NADH-diaphorase is active during selective phases of the cell cycle in mouse neuroblastoma cell line NB41A3. Its relation to cell growth and differentiation

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