AI Article Synopsis
- A new compound called TPP2a was created by attaching a triphenylphosphine (TPP) group to an existing thioredoxin reductase (TrxR) inhibitor, enhancing its ability to target mitochondria in cells.
- TPP2a effectively inhibits TrxR in HeLa cancer cells, resulting in increased levels of reactive oxygen species (ROS) and triggering cell death through mitochondrial apoptosis.
- This compound shows significantly stronger anticancer effects compared to the original inhibitor, and its specific interaction with mitochondrial TrxR can be confirmed using fluorescent microscopy and a novel labeling strategy in complex biological environments.
Article Abstract
A mitochondria-targeted approach was developed to increase the cellular bioactivities of thioredoxin reductase (TrxR) inhibitors. By being conjugated with a triphenylphosphine (TPP) motif to a previously found TrxR inhibitor 2a, the resulted compound TPP2a can target subcellular mitochondria and efficiently inhibit cellular TrxR, leading to remarkably increased cellular ROS level and mitochondrial apoptosis of HeLa cancer cells. The cellular bioactivities of TPP2a, including its cytotoxicity against a panel of cancer cell lines, dramatically elevated compared with its parental compound 2a. The selectively and covalently interaction of TPP2a with subcellular mitochondrial TrxR was validated by fluorescent microscopy. Moreover, a nonspecific signal quenching coupled strategy was proposed based on the environmentally sensitive fluorescence of TPP2a, which makes it possible to label TrxR by removing the nonspecific backgrounds caused by TPP2a under complex biosettings such as cellular lysates and living cells, implicating a potential of TPP2a for TrxR-specific labeling.
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| http://dx.doi.org/10.1021/acschembio.5b00708 | DOI Listing |
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