Title |
Mitochondria-Targeted Drugs Synergize with 2-Deoxyglucose to Trigger Breast Cancer Cell Death
|
---|---|
Published in |
Cancer Research, May 2012
|
DOI | 10.1158/0008-5472.can-11-3928 |
Pubmed ID | |
Authors |
Gang Cheng, Jacek Zielonka, Brian P. Dranka, Donna McAllister, A. Craig Mackinnon, Joy Joseph, Balaraman Kalyanaraman |
Abstract |
Cancer cells are long known to exhibit increased aerobic glycolysis, but glycolytic inhibition has not offered a viable chemotherapeutic strategy in part because of the systemic toxicity of antiglycolytic agents. However, recent studies suggest that a combined inhibition of glycolysis and mitochondrial function may help overcome this issue. In this study, we investigated the chemotherapeutic efficacies of mitochondria-targeted drugs (MTD) in combination with 2-deoxy-d-glucose (2-DG), a compound that inhibits glycolysis. Using the MTDs, termed Mito-CP and Mito-Q, we evaluated relative cytotoxic effects and mitochondrial bioenergetic changes in vitro. Interestingly, both Mito-CP and Mito-Q synergized with 2-DG to decrease ATP levels in two cell lines. However, with time, the cellular bioenergetic function and clonogenic survival were largely restored in some cells. In a xenograft model of human breast cancer, combined treatment of Mito-CP and 2-DG led to significant tumor regression in the absence of significant morphologic changes in kidney, liver, or heart. Collectively, our findings suggest that dual targeting of mitochondrial bioenergetic metabolism with MTDs and glycolytic inhibitors such as 2-DG may offer a promising chemotherapeutic strategy. |
X Demographics
As of 1 July 2024, you may notice a temporary increase in the numbers of X profiles with Unknown location. Click here to learn more.
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Japan | 2 | 1% |
United Kingdom | 2 | 1% |
United States | 2 | 1% |
Russia | 1 | <1% |
Unknown | 161 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 44 | 26% |
Researcher | 42 | 25% |
Student > Master | 12 | 7% |
Student > Bachelor | 10 | 6% |
Professor > Associate Professor | 8 | 5% |
Other | 23 | 14% |
Unknown | 29 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 46 | 27% |
Biochemistry, Genetics and Molecular Biology | 34 | 20% |
Medicine and Dentistry | 19 | 11% |
Chemistry | 12 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 9 | 5% |
Other | 16 | 10% |
Unknown | 32 | 19% |