|
|
Home > Blog - Impact of Novel MDR Modulators on Human Can
| | |
|
Blog - Impact of Novel MDR Modulators on Human Cancer Cells: Reversal Activities and Induction Studies
Last Updated October 30, 2008
|
|
PURPOSE: Novel multidrug resistance (mdr) modulators have been proved as inhibitors of P-glycoprotein (P-gp). We first investigated the in vitro effects of selected compounds in human cancer cells on multidrug resistance reversal effects compared to drug standards and on P-gp induction to characterize the potential of the compounds as clinical candidates.
METHODS: The uptake of daunorubicin into a parental cancer cell line and P-gp expressing subcell line in presence of the modulators was characterized by flow cytometry. Induction of P-gp was investigated in P-gp expressing and non-expressing cancer cell lines on the RNA level by real-time quantitive polymerase chain reaction (RTQ-PCR) and protein quantification.
RESULTS: The novel modulators showed activities as mdr reversers in a P-gp specific human cancer cell model with mainly increased uptake rates of daunorubicin into the drug-resistant cell line. H17 proved to be more active than cyclosporine A as a known strong mdr modulator. The induction studies revealed practically no induction potential of the compounds in usual short-time drug application regimes in cell lines. Furthermore, the novel modulators did not increase the efflux of a P-gp model substrate in the functionality model assay. This confirmed the results of non-P-gp induction which was observed on both the RNA and the protein levels.
CONCLUSIONS: The novel mdr modulators proved as perspective candidates for further clinical studies because they turned out to be highly active in human cancer cell models. Furthermore, they showed no potential to induce the transmembrane efflux pump P-gp. This is a significant advantage compared to modulators which failed in clinical trials because of induction-effects that increase cellular resistances and, moreover, side effects in normal cells.
|
Posted by C. Coburger, H. Lage, J. Molnár and A. Hilgeroth on October 30, 2008 |
| Comments 0 of 0 |
|
If you would like to comment on this post, please fill out the form below.
|
* denotes required field
Post Your Comments On*
Comment*
99999 characters remaining
|
| *All comments will undergo a review process before they are posted online. This is to prevent spam and ads from being posted. Thank you for your time and patience. |
Opinions expressed on the ACC Corporation Blog and all corresponding comments are the individual opinions of the original authors and don’t in any way reflect the opinions of ACC Corporation. |
|
| |
| |
| | |
|
You must be logged in to view your shopping cart information
We accept all major credit cards
We have clients in over
75 countries spanning 5
continents
Advertise with American Custom Chemical Corporations. We make it beneficial and profitable for you to work with us.
To track your order please click on the shipping options below
For the latest updates on industry information and news
|
|