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Energy network within cells may be new target for cancer therapy
Date:2/21/2012

ivision cycle comes to a halt if the mitochondria are prevented from dividing. This new therapy may be especially useful in cancers which become resistant to conventional chemotherapy that directly targets the cycle."

The researchers found that the mitochondrial networks within several different lung cancer cell lines were highly fragmented, compared to normal lung cells. Cancer cells had low levels of mitofusin-2 (Mfn-2), a protein that promotes fusion by tethering adjacent mitochondria, and high levels of dynamin-related protein (Drp-1), which initiates fission by encircling the organelle and squeezing it into two discrete fragments. The Drp-1 in cancer cells also tended to be in its most active form.

The researchers tested several ways to enhance fusion and restore the mitochondrial network, both in cell culture and in animal models. They used gene therapy to increase the expression of Mfn-2, injected a small molecule (mdivi-1) that inhibits Drp-1, and used genetic techniques to block the production of Drp-1. All three interventions markedly reduced mitochondrial fragmentation, increased networking and reduced cancer cell growth.

Although the authors identify mitochondrial fission and Drp-1 activation as a potential therapeutic target in lung cancer, "this is not a cure," Archer emphasized. The treatment drastically reduced tumor size but the tumors did not completely disappear. They continued to use high levels of glucose as fuel, a hallmark of cancer metabolism that can be seen on PET scans. "This remnant could be either a central cluster of cancer stem cells," Archer said, "or an inflammatory response, the immune system infiltrating the tumor."

"Inhibiting mitochondrial fission", Archer said, "did not show any significant toxicity in mice or rats, so we are quite optimistic that our findings can lead to the development of novel, clinically feasible therapies."

The substances used to block fusion are commercially av
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Contact: John Easton
john.easton@uchospitals.edu
773-795-5225
University of Chicago Medical Center
Source:Eurekalert

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