PHILADELPHIAResearchers from Jefferson's Kimmel Cancer Center have genetic evidence suggesting the antioxidant drugs currently used to treat lung disease, malaria and even the common cold can also help prevent and treat cancers because they fight against mitochondrial oxidative stressa culprit in driving tumor growth.
For the first time, the researchers show that loss of the tumor suppressor protein Caveolin-1 (Cav-1) induces mitochondrial oxidative stress in the stromal micro-environment, a process that fuels cancer cells in most common types of breast cancer.
"Now we have genetic proof that mitochondrial oxidative stress is important for driving tumor growth," said lead researcher Michael P. Lisanti, M.D., Ph.D., professor of cancer biology at Jefferson Medical College of Thomas Jefferson University and member of the Kimmel Cancer Center at Jefferson. "This means we need to make anti-cancer drugs that specially target this type of oxidative stress. And there are already antioxidant drugs out there on the market as dietary supplements, like N-acetyl cysteine."
These findings were published in the online February 15 issue of Cancer Biology & Therapy.
Lisanti's lab previously discovered Cav-1 as a biomarker that functions as a tumor suppressor and is the single strongest predictor of breast cancer patient outcome. For example, if a woman has triple negative breast cancer and is Cav-1 positive in the stroma, her survival is greater than 75 percent at 12 years, versus less than 10 percent at 5 years if she doesn't have the Cav-1 protein, according to Dr. Lisanti.
The researchers also established Cav-1's role in oxidative stress and tumor growth; however, where that stress originates and its mechanism(s) were unclear.
To determine this, Jefferson researchers applied a genetically tractable model for human cancer associated fibroblasts in this study using a targeted sh-RNA knock-down approach. Withou
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Thomas Jefferson University