Combating Multidrug Resistance

On Friday, March 31, 2023, the UH Drug Discovery Institute hosted Zhe-Sheng Chen, Ph.D.

April 12, 2023 /

Wei Wang, Ph.D.

 Cancer cells and DNA strands


Chen, from St. John’s University in New York, gave a presentation on multidrug resistance (MDR), a phenomenon that represents a major obstacle to the treatment of cancer. Understanding the resistance mechanisms and how to reverse this resistance hold the promise of improvements in the use of currently available anticancer drugs. 

The seminar, titled "Cycloruthenated Self-Assembly with Metabolic Inhibition to Efficiently Overcome Multidrug Resistance in Cancers," focused on the synthesis and evaluation of the efficacy of a cycloruthenated complex called RuZ in overcoming multidrug resistance (MDR) in cancer cells. RuZ has the unique ability to self-assemble into nanoaggregates within the cell culture medium, resulting in a high intracellular concentration of RuZ in MDR cancer cells. This self-assembly process significantly reduces oxygen consumption and inhibits glycolysis, leading to decreased cellular adenosine triphosphate (ATP) levels. The decrease in ATP levels, combined with RuZ's low affinity for the ABCB1 and ABCG2 transporters (which mediate MDR), enhances the retention of RuZ within MDR cancer cells.

Furthermore, RuZ induces cellular oxidative stress, leading to DNA damage and increased apoptosis of cancer cells. Proteomic profiling analysis suggests that RuZ primarily downregulates proteins involved in glycolysis and aerobic mitochondrial respiration, while upregulating proteins involved in apoptosis. These findings represent a groundbreaking discovery, demonstrating the efficacy of self-assembled cycloruthenated complexes in inhibiting the growth of MDR cancer cells.

 Moreover, Chen, who serves as the editor-in-chief of the high-impact journal Drug Resistance Updates (impact factor: 22.8), also shared invaluable techniques and strategies for successful publication in prestigious journals during the seminar.

Zhe-Sheng Chen is a professor, director of the Institute for Biotechnology and special advisor to the provost for international students at St. John’s University. He is an expert in the field of multi-drug resistance (MDR) following chemotherapy. His lab is hastening the development of more effective anticancer drugs. His research interests range from basic to clinical studies on drug resistance in cancers.


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