Novel protein for cancer gene therapy
doi:10.1038/nindia.2013.7 Published online 18 January 2013
In a discovery that could result in gene therapy for cancer, researchers in New Delhi have identified synthesis of cytochrome-c oxidase — otherwise known as SCO2 — as a potential tumour suppressor gene1.
"Our study established SCO2 as an apoptotic protein which has potential to function as an anti-cancer gene therapy molecule," Uttam Pati, who led the research told Nature India.
Apoptosis, or programmed cell death, is a natural process that allows old cells to die so that new cells can replace them. In cancer, too little apoptosis occurs resulting in malignant cells not dying. So, there is an imbalance between cell division and cell death. Cells that should die fail to receive signals to do so. This results in uncontrolled cell growth. Apoptosis is a popular target of treatment in cancer. Pati and co-workers have shown in mice that SCO2 behaves as an apoptotic protein and can be a potential molecule for gene therapy.
"The SCO2 gene therapy conducted by exogenous addition of SCO2 gene into both breast and colon tumours resulted in the consistent regression of these tumour xenografts in mice," the researchers reported. They found that combining their SCO2 gene therapy with known anti cancer drugs cisplatin or tamoxifen resulted in more than 85% tumour regression in four weeks.
SCO2 regressed the tumour in mice by increasing the generation of 'reactive oxygen species'(ROS), toxic to cancer cells, and by activating the 'Apoptosis Signal-regulating Kinase 1 (ASK1)', a pathway to apoptosis.
"The cancer cell normally consumes oxygen in a glycolysis pathway in contrast to normal tissue that gets oxygen supply through oxidative phosphorylation pathway," Pati explains. "The role of this SCO2 gene in helping the cancer cell to reverse the glycolytic pathway will be very useful in future gene therapy protocol", he says.
The authors of this work are from: Jawaharlal Nehru Univeristy, New Delhi and Chhatrapati Shahuji Maharaj Medical University, Lucknow, India; and Ohio State University Medical Centre, Columbus, Ohio, USA.
- Madan, E. et. al. SCO2 induces p53-mediated apoptosis by Thr845 phosphorylation of ASK-1 and dissociation of ASK-1-TRX complex. Mol. Cell. Biol. doi: 10.1128/MCB.06798-11 (2013)