Cervical cancer is the second most common malignancy in women with over half a million cases occurring worldwide each year. Despite multi-modal approaches, this disease remains highly resistant and novel approaches for treatment are urgently needed.
The cytotoxic effect of photo-excited titanium dioxide (TiO2) by far UV (254 nm) illumination, creating reactive oxygen species (ROS), has been examined in several cancer models in vitro. However, serious damage to the surround healthy cells limits the applicability of this approach. Thus, developing a technique that will achieve TiO2 photoxidative effect at the visible or near UV (>300 nm) range, causing less damage to the healthy is preferred.
Our group has recently discovered a unique protein that binds strongly TiO2. This protein, dihydrolipoamide dehydrogenase (DLDH) is critical for energy and redox balance in the cell. Illumination of DLDH, independently, results in elevated levels of ROS. In addition, bioinformatics analysis has suggested that DLDH is a homologue of AIF (Apoptosis-inducing factor), a central player in apoptosis.
Cervical cancer cells overexpress the cell surface receptor ?v?3 integrin, which interacts with proteins of the extra cellular matrix through an RGD (Arg-Gly-Asp) recognition site. We bio-engineered the human DLDH with RGD tails (RGD2-DLDH) and generated a protein capable of serving as a bridge between the integrin expressing cancer cell and the TiO2 in its natural and nanostructure forms. We propose that illumination of this complex (RGD2-DLDH-TiO2) will produce high ROS activity and cancer cell death and may serve as a "neo-radiation" targeted treatment in cervical cancer. We believe that the understanding gained from this work will be relevant to other integrin-expressing tumor models that have not been tested so far.
Project ID : 8-2014-758
Cervical cancer is the second most common malignancy in women with over half a million cases occurring worldwide each year. Despite multi-modal approaches, this disease remains highly resistant and novel approaches for treatment are urgently needed.
The cytotoxic effect of photo-excited titanium dioxide (TiO2) by far UV (254 nm) illumination, creating reactive oxygen species (ROS), has been examined in several cancer models in vitro. However, serious damage to the surround healthy cells limits the applicability of this approach. Thus, developing a technique that will achieve TiO2 photoxidative effect at the visible or near UV (>300 nm) range, causing less damage to the healthy is preferred.
Our group has recently discovered a unique protein that binds strongly TiO2. This protein, dihydrolipoamide dehydrogenase (DLDH) is critical for energy and redox balance in the cell. Illumination of DLDH, independently, results in elevated levels of ROS. In addition, bioinformatics analysis has suggested that DLDH is a homologue of AIF (Apoptosis-inducing factor), a central player in apoptosis.
Cervical cancer cells overexpress the cell surface receptor ?v?3 integrin, which interacts with proteins of the extra cellular matrix through an RGD (Arg-Gly-Asp) recognition site. We bio-engineered the human DLDH with RGD tails (RGD2-DLDH) and generated a protein capable of serving as a bridge between the integrin expressing cancer cell and the TiO2 in its natural and nanostructure forms. We propose that illumination of this complex (RGD2-DLDH-TiO2) will produce high ROS activity and cancer cell death and may serve as a "neo-radiation" targeted treatment in cervical cancer. We believe that the understanding gained from this work will be relevant to other integrin-expressing tumor models that have not been tested so far.
Project manager
Rona Samler
VP, BD Physical Science, Medical Device, Chemistry
Project researchers
Gideon Fleminger
T.A.U Tel Aviv University, Life Sciences
Molecular Microbiology-Biotechnology
Osnat Ashur-Fabian
,
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