Related Experiment Video
Updated: Mar 13, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Identification and Validation of Compounds Selectively Killing Resistant Cancer: Delineating Cell Line-Specific
András Füredi1, Szilárd Tóth1, Kornélia Szebényi2
1Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary.
Abstract:
Despite significant progress, resistance to chemotherapy is still the main reason why cancer remains a deadly disease. An attractive strategy is to target the collateral sensitivity of otherwise multidrug resistant (MDR) cancer. In this study, our aim was to catalog various compounds that were reported to elicit increased toxicity in P-glycoprotein (Pgp)-overexpressing MDR cells. We show that the activity of most of the serendipitously identified compounds reported to target MDR cells is in fact cell-line specific, and is not influenced significantly by the function of Pgp. In contrast, novel 8-hydroxyquinoline derivatives that we identify in the National Cancer Institute (NCI) drug repository possess a robust Pgp-dependent toxic activity across diverse cell lines. Pgp expression associated with the resistance of the doxorubicin-resistant Brca1-/-;p53-/- spontaneous mouse mammary carcinoma cells could be eliminated by a single treatment with NSC57969, suggesting that MDR-selective compounds can effectively revert the MDR phenotype of cells expressing Pgp at clinically relevant levels. The discovery of new MDR-selective compounds shows the potential of this emerging technology and highlights the 8-hydroxyquinoline scaffold as a promising starting point for the development of compounds targeting the Achilles heel of drug-resistant cancer. Mol Cancer Ther; 16(1); 45-56. ©2016 AACR.
Insights
New 8-hydroxyquinoline derivatives show potent activity against multidrug-resistant (MDR) cancer by targeting P-glycoprotein (Pgp). This discovery offers a promising strategy to overcome chemotherapy resistance and treat aggressive cancers.
Area of Science:
- Cancer Research
- Pharmacology
- Drug Discovery
Background:
- Chemotherapy resistance remains a major obstacle in cancer treatment.
- Targeting collateral sensitivity in multidrug-resistant (MDR) cancer presents a viable therapeutic strategy.
- P-glycoprotein (Pgp) is a key mediator of MDR, pumping drugs out of cancer cells.
Purpose of the Study:
- To identify compounds that specifically increase toxicity in Pgp-overexpressing MDR cancer cells.
- To evaluate the Pgp-dependency of identified compounds' activity.
- To explore the potential of novel chemical scaffolds for overcoming MDR.
Main Methods:
- Screened compounds from the National Cancer Institute (NCI) drug repository.
- Assessed compound activity in various cancer cell lines, including Pgp-overexpressing models.
- Utilized doxorubicin-resistant Brca1-/-;p53-/- mouse mammary carcinoma cells to evaluate Pgp-dependent effects.
Main Results:
- Most previously reported MDR-targeting compounds showed cell-line specific activity, independent of Pgp.
- Novel 8-hydroxyquinoline derivatives demonstrated robust Pgp-dependent toxicity across diverse cell lines.
- Treatment with NSC57969 (an 8-hydroxyquinoline derivative) eliminated Pgp expression and reverted the MDR phenotype in resistant mouse carcinoma cells.
Conclusions:
- 8-hydroxyquinoline derivatives are effective MDR-selective compounds targeting Pgp.
- These compounds can reverse Pgp-mediated multidrug resistance at clinically relevant levels.
- The 8-hydroxyquinoline scaffold is a promising starting point for developing new drugs against drug-resistant cancers.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:56Treatment Resistant Cancers
02:56Treatment Resistent Cancers