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Biomedical subjects

M Israel

Publications and source records attributed to M Israel.

152 records · Page 9Linked to original sources
PubMedDate not supplied

Mass spectral characterization of three anthracycline antibiotics: a comparison of thermospray mass spectrometry to particle beam mass spectrometry.

Mass spectral results for three anthracyclines, doxorubicin, daunorubicin, and carminomycin are compared by using thermospray (TS) or particle beam (PB) [electron ionization (EI) and chemical ionization (CI)] instruments. Typically, positive ion TS mass spectrometry (MS) provided intense [MH]+ ions and some fragment ions, while PBMS in the EI mode provided only fragment ions. Significant [MH]+ ions were observed for carminomycin and daunorubicin when analyzed using PBMS in the positive ion CI mode. Under negative ion detection, TSMS yielded intense [M-H]- ions for these compounds while PBCIMS resulted in significant M- ions. Fragment ions observed in all three anthracyclines under positive and negative ion detection by TSMS and PBCIMS are due mainly to the cleavage of glycosidic bond, loss of H2O, and the loss of the side chain (COCH2R2) from the aglycone.

Carubicin↗
PubMedDate not supplied

Cremophor EL inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced protein phosphorylation in human myeloblastic leukemia ML-1 cells.

Cremophor EL, a polyloxyethylene castor oil derivative used clinically as a parenteral vehicle, inhibits protein kinase c activity in vitro. The tumor promoting agent TPA (12-0-tetradecanoylphorbol-13-acetate) activated protein kinase C and induced phosphorylation of cellular proteins of human myeloblastic leukemia ML-1 cells. Polypeptides of 56 KDa, 44 KDa, 37 KDa, 35 KDa and 31 KDa were particularly phosphorylated in response to TPA activation. However, the phosphorylations of these polypeptides, especially that of 37 KDa, were greatly reduced by treatment of the TPA-activated ML-1 cells with Cremophor EL. Cremophor EL also inhibited the growth of ML-1 cells. On the other hand, the TPA-induced cell differentiation in ML-1, which is considered a separate event from protein kinase C activation, was not affected by Cremophor EL. These studies suggest biological implications for the observed in vitro activity of Cremophor EL. The studies may also provide a mechanism for the Cremophor EL-associated cytotoxicities observed when it is used clinically as a parenteral vehicle.

Cell Line↗
PubMedDate not supplied

Adriamycin interacts with diacylglycerol to inhibit human leukemia protein kinase C.

Protein kinase C (PKC) from human leukemia ML-1 cells was found to be susceptible to inhibition by the antineoplastic anthracycline adriamycin (ADR). Half-maximal inhibition (IC50 value) was observed at 200 microM. However, preincubation of ADR with phosphatidylserine (PS) or PKC enzyme, prior to the enzyme assay, reduced the IC50 value from 200 microM to 52 microM or 40 microM, respectively, indicating an affinity of ADR for PS, and also a possible action site for ADR on PKC molecules. Preincubation of ADR with diacylglycerol (DAG) before the PKC assay resulted in a more pronounced effect, i.e., a more rapid decline of PKC activity with an IC50 value of 7 microM. However, the IC50 for ADR inhibition was not altered when ATP, histone or Ca++ were preincubated with ADR. Studies of the kinetic nature of the inhibition revealed that ADR inhibition assumes competitive kinetics with respect to DAG. Therefore, the mechanism by which ADR inhibits PKC activity may involve a multi-site action: a primary interaction with DAG, and a secondary lower interaction with membrane PS and PKC apoenzyme.

Binding Sites↗
PubMedDate not supplied

Mechanistic studies on N-benzyladriamycin-14-valerate (AD 198), a highly lipophilic alkyl adriamycin analog.

AD 198, a novel lipophilic N-alkyl derivative of adriamycin (ADR) and a potential anticancer agent for preclinical development, was studied for its effects on the activities of DNA and RNA polymerases in vitro and its ability to bind DNA. AD 198, which contains a benzyl substituent on the glycosidic amine, was found to interact with DNA through drug-DNA binding to an extent less than its parent compound ADR as shown by fluorescent emission spectra studies. It had a preferential inhibitory effect against RNA vs. DNA synthesis in vitro by RNA or DNA polymerases from both E. coli and chicken leukemia cells. Preincubation studies indicated that AD 198 may inhibit the activity of E. coli RNA polymerase through drug-template interaction and that of leukemic RNA polymerase, which uses single stranded DNA as template, through enzyme inactivation.

Animals↗