PMID: 9639395Jun 25, 1998Paper

Reversal of multidrug resistance by the staurosporine derivatives CGP 41251 and CGP 42700

International Journal of Cancer. Journal International Du Cancer
I UtzJ Hofmann

Abstract

It has been shown previously that the staurosporine derivative CGP 41251, a specific inhibitor of protein kinase C (IC50 = 50 nM), exhibits antitumor activity and reverses mdr1 mediated multidrug resistance. At present, the compound is evaluated as an anticancer drug in clinical phase I trials. We compared the effects of CGP 41251 with CGP 42700, another staurosporine derivative, which exhibits low protein kinase C inhibiting activity (IC50 = > 100 microM). We found that in contrast to CGP 41251, CGP 42700 does not show antiproliferative activity in HeLa and KB cells in tissue culture (up to a concentration of 10 microM). We compared both compounds for their ability to reverse mdr1-mediated resistance in KB-C1 and in HeLa-MDR1 cells (transfected with the mdr1 gene). CGP 42700 is able to reverse mdr1-mediated resistance to a similar extent as CGP 41251. The intracellular accumulation of rhodamine 123 in KB-C1 cells following pretreatment with CGP 41251 for 30 min was higher than that following treatment with CGP 42700 if determined in medium without serum. However, quantitation of rhodamine efflux in an ex vivo assay using human CD8+ cells in serum showed that CGP 42700 is more effective in inhibiting the efflux of rhodamine 123...Continue Reading

References

Jan 1, 1992·Journal of Cancer Research and Clinical Oncology·J HofmannH Grunicke
Apr 1, 1991·International Journal of Cancer. Journal International Du Cancer·J HofmannH Grunicke
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K E NoonanI B Roninson
Apr 1, 1994·International Journal of Cancer. Journal International Du Cancer·I UtzJ Hofmann
Jan 19, 1996·The Journal of Biological Chemistry·U A GermannM M Gottesman

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Citations

Apr 15, 2010·Marine Drugs·Sheila Marie Pimentel-ElardoUte Hentschel
Jun 11, 2003·Journal of Clinical Pharmacy and Therapeutics·R B WangE J Lien
Oct 1, 2005·Cancer Investigation·Isa E L M KuppensJ H M Schellens
May 3, 2003·Journal of Experimental Therapeutics & Oncology·John A Kellen

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