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Anthracycline drug targeting: cytoplasmic versus nuclear--a fork in the road.
- L. Lothstein, M. Israel, T. Sweatman
- Biology, ChemistryDrug resistance updates : reviews and…
- 1 June 2001
This review will present recent strategies in anthracycline design and assess their potential therapeutic merits, including cytoplasmic or nuclear sites.
Clinical evaluation of long-term, continuous-infusion doxorubicin.
DNA topoisomerase II-mediated interaction of doxorubicin and daunorubicin congeners with DNA.
The study shows that DNA intercalation is required but not sufficient for the activity by topo-II-targeted anthracyclines, and may provide guidance for the synthesis and development of new active analogues.
N-benzyladriamycin-14-valerate (AD 198) activates protein kinase C-δ holoenzyme to trigger mitochondrial depolarization and cytochrome c release independently of permeability transition pore opening…
- L. Lothstein, L. Savranskaya, C. Barrett, M. Israel, T. Sweatman
- Biology, ChemistryAnti-cancer drugs
- 1 June 2006
Examination of AD 198-induced apoptosis in 32D.3 mouse myeloid cells suggests that PTPC-independent mitochondrial activation by AD 198 is consistent with the inability of B cl-2 and Bcl-XL expression to block AD 198's apoptosis.
Circumvention of P-GP MDR as a function of anthracycline lipophilicity and charge.
It is shown that highly lipophilic anthracyclines are shown to circumvent MDR which most likely reflects their ability to localize in the cytoplasm and affect targets other than nuclear DNA, i.e., mitochondria, and to act as self modulators of MDR.
ATM and the Catalytic Subunit of DNA-Dependent Protein Kinase Activate NF-κB through a Common MEK/Extracellular Signal-Regulated Kinase/p90rsk Signaling Pathway in Response to Distinct Forms of DNA…
It is suggested that distinct members of the phosphatidylinositol kinase family activate a common prosurvival MAPK/IKK/NF-κB pathway that opposes the apoptotic response following DNA damage.
Metabolism and elimination of rhodamine 123 in the rat
The plasma decay and the biliary and urinary elimination of parent drug and metabolites in female Sprague-Dawley rats receiving RH-123 at an intravenous dose equivalent to the therapeutic dose used in murine tumor models was examined using a high-performance liquid chromatographic assay system with fluorescence detection.
Novel extranuclear-targeted anthracyclines override the antiapoptotic functions of Bcl-2 and target protein kinase C pathways to induce apoptosis.
It is suggested that AD 198 induces mitochondrial-dependent apoptosis in 32D.3 cells by activating PKC-delta holoenzyme on mitochondria, which, in turn, overrides the antiapoptotic effects of Bcl-2.
Interaction of the novel anthracycline antitumor agent N-benzyladriamycin-14-valerate with the C1-regulatory domain of protein kinase C: structural requirements, isoform specificity, and correlation…
Anthracycline antibiotics like doxorubicin (DOX) are known to exert their antitumor effects primarily via DNA intercalation and topoisomerase II inhibition. By contrast, the noncross-resistant…
Protein-associated DNA breaks and DNA-protein cross-links caused by DNA nonbinding derivatives of adriamycin in L1210 cells.
- M. Levin, R. Silber, M. Israel, A. Goldfeder, V. Khetarpal, M. Potměšil
- Chemistry, BiologyCancer research
- 1 March 1981
The similar effects on DNA macromolecules, observed between intercalating and non-DNA-binding anthracyclines, are consistent with the concept that mechanisms other than direct interaction with DNA play a role in the toxic effects of these compounds.