Exploiting mitochondrial targeting signal(s), TPP and bis‐TPP, for eradicating cancer stem cells (CSCs)
06-01-2018TPP-related compounds may provide a novel chemical strategy for effectively targeting bulk cancer cells and CSCs, while minimizing off-target side-effects in normal cells.
Several independent lines of evidence support the idea that increased mitochondrial biogenesis or higher levels of mitochondrial protein translation may occur in CSCs.
For example, unbiased proteomics analysis directly shows that mitochondrial mass is elevated in CSCs.
High telomerase activity also directly correlated with high mitochondrial mass and the ability of CSCs to undergo proliferative expansion.
Similarly, high mitochondrial mass in CSCs was also specifically associated with mitochondrial ROS production and could be targeted with either: i) mitochondrial anti-oxidants, ii) inhibitors of mitochondrial biogenesis or OXPHOS, and even iii) inhibitors of cell proliferation.
Here, the researchers explored the hypothesis that TPP related compounds could be utilized to inhibit mitochondria in cancer stem cells.
Interestingly, these TPP related compounds were nontoxic and had little or no effect on ATP production in normal human fibroblasts, but selectively targeted adherent bulk cancer cells.
Therefore, these TPP related compounds successfully inhibited anchorage independent growth, which is normally associated with a metastatic phenotype.
In summary, the researchers showed that TPP related compounds provide a novel chemical strategy for effectively killing both i) bulk cancer cells and ii) CSCs, while specifically minimizing or avoiding off target side effects in normal cells.
Full text - http://www.aging-us.com/article/101384/text
Correspondence to - Michael P. Lisanti, Federica Sotgia; email: Michaelp.lisanti@gmail.com, fsotgia@gmail.com
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