Navigation Links
USC researchers determine mechanism of action of chemotherapy drug

The chemotherapy drug motexafin gadolinium (brand name: Xcytrin, manufactured by Pharmacyclics, Inc.) works to thwart cancer cells by disrupting key enzymes involved in cellular metabolism, according to a team of researchers led by Joseph Hacia, Ph.D., assistant professor of biochemistry and molecular biology at the Keck School of Medicine of the University of Southern California.

The cellular disruption results in increases in the amount of zinc available inside the cancer cells, and because zinc is involved in protein structure and function, leads to inhibition of enzyme activity and to the death of the cells.

A paper describing these findings was published in the May 1, 2005, issue of the journal Cancer Research.

In order to gain a better understanding of the mechanism of action of this novel chemotherapeutic agent, the researchers looked at gene expression profiles and other biochemical properties of cells from human lung, prostate and lymphoma cancer cell cultures that had been treated with motexafin gadolinium, or MGd. What they found was that the drug created oxidative stress in the tumor cells, increasing the levels of expression of the genes that produce metallothioneins.

The researchers showed that the increased metallothionein expression levels resulted from significantly increased levels of free-i.e., not protein-bound-zinc in the cells. The zinc, in turn, acted to inhibit an enzyme-thioredoxin reductase-that is an important component in the cell's antioxidant system, as well as important in DNA synthesis. In other words, thioredoxin reductase is key to the replication and survival of cells, and its inhibition ultimately leads to cell death.

"Our studies showed that MGd induces oxidative stress in cancer cells," says Hacia, who is a member of USC's Institute for Genetic Medicine, "and this leads to disruption of zinc metabolism and alteration of key enzymes and metabolites necessary for normal cell function."

< p>Thus, the researchers noted, the use of MGd leads to the death of cancer cells via disruption of critical enzymes needed for cell survival and replication.

"We have increased the understanding of this drug's mechanism of action," Hacia said of the study, adding that it also may "provide support for the hypothesis that agents that disrupt metabolism and increase intracellular zinc levels have potential applications as anticancer therapeutics."


Source:University of Southern California

Related biology news :

1. NYU researchers simulate molecular biological clock
2. Vital step in cellular migration described by UCSD medical researchers
3. ASU researchers finds novel chemistry at work to provide parrots vibrant red colors
4. UCSD researchers maintain stem cells without contaminated animal feeder layers
5. Why do insects stop breathing? To avoid damage from too much oxygen, say researchers
6. New protein discovered by Hebrew University researchers
7. First real-time view of developing neurons reveals surprises, say Stanford researchers
8. Agilent Technologies releases automated literature search tool for biology researchers
9. Self-assembled nano-sized probes allow Penn researchers to see tumors through flesh and skin
10. Yale researchers identify molecule for detecting parasitic infection in humans
11. US life expectancy about to decline, researchers say
Post Your Comments:

(Date:6/16/2016)... , June 16, 2016 ... size is expected to reach USD 1.83 billion ... Grand View Research, Inc. Technological proliferation and increasing ... applications are expected to drive the market growth. ... , The development of advanced multimodal ...
(Date:6/9/2016)... June 9, 2016  Perkotek an innovation leader in attendance control systems is proud ... work hours, for employers to make sure the right employees are actually signing in, ... ... ... ...
(Date:6/7/2016)... , June 7, 2016  Syngrafii Inc. and ... business relationship that includes integrating Syngrafii,s patented LongPen™ ... project. This collaboration will result in greater convenience ... credit union, while maintaining existing document workflow and ... ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... ... its second eBook, “Clinical Trials Patient Recruitment and Retention Tips.” Partnering with experienced ... this eBook by providing practical tips, tools, and strategies for clinical researchers. , ...
(Date:6/23/2016)... 2016 Houston Methodist Willowbrook Hospital has ... Association to serve as their official health care ... Willowbrook will provide sponsorship support, athletic training services, ... coaches, volunteers, athletes and families. "We ... Association and to bring Houston Methodist quality services ...
(Date:6/23/2016)... ... ... Supplyframe, the Industry Network for electronics hardware design and ... in Pasadena, Calif., the Design Lab’s mission is to bring together inventors and ... brought to market. , The Design Lab is Supplyframe’s physical representation of one ...
(Date:6/23/2016)... Andrew D Zelenetz ... Published recently in Oncology ... touchONCOLOGY, Andrew D Zelenetz , discusses the ... is placing an increasing burden on healthcare systems ... With the patents on many biologics expiring, interest ...
Breaking Biology Technology: